Apoptosis is vital for improving the efficacy of lung cancer (LC) immunotherapy by targeting cancer cell elimination. Despite its importance, there is a lack of comprehensive bibliometric studies analyzing global research on apoptosis in LC immunotherapy. This analysis aims to address this gap by highlighting key trends, contributors, and future directions. A total of 969 publications from 1996 to 2024 were extracted from the Web of Science Core Collection. Analysis was conducted using VOSviewer, CiteSpace, and the R package 'bibliometrix.' The study included contributions from 6,894 researchers across 1,469 institutions in 61 countries, with research published in 356 journals. The volume of publications has steadily increased, led by China and the United States, with Sichuan University as the top contributor. The journal Cancers published the most articles, while Cancer Research had the highest co-citations. Yu-Quan Wei was the leading author, and Jemal, A. was the most frequently co-cited. Key research themes include "cell death mechanisms," "immune regulation," "combination therapies," "gene and nanomedicine applications," and "traditional Chinese medicine (TCM)." Future research is likely to focus on "coordinated regulation of multiple cell death pathways," "modulation of the tumor immune microenvironment," "optimization of combination therapies," "novel strategies in gene regulation," and the "integration of TCM" for personalized treatment. This is the first bibliometric analysis on the role of apoptosis in LC immunotherapy, providing an landscape of global research patterns and emerging therapeutic strategies. The findings offer insights to guide future research and optimize treatment approaches.

Initial immunotherapy outcomes with toripalimab suggest a potential paradigm shift in the treatment of advanced triple-negative breast cancer (TNBC), promising extended survival for patients. However, its cost-effectiveness in the treatment of TNBC within the US health care context remains to be determined.

A 5-year Markov model was developed using data from the TORCHLIGHT study to evaluate the cost-effectiveness of toripalimab plus nab-paclitaxel as a first-line therapy for metastatic or recurrent TNBC in the US. The model incorporated efficacy and safety data, literature-derived costs and utilities, and calculated ICERs. Sensitivity analyses were conducted to assess the impact of variable uncertainties on the outcomes.

Toripalimab combined with nab-P chemotherapy for TNBC patients resulted in an additional 2.68 life years (LYs) and 1.72 quality-adjusted life years (QALYs), with an ICER of $593,750 per QALY. Sensitivity analyses indicated that the cost and survival utility of toripalimab significantly influence patient outcomes. At a $100,000/QALY WTP threshold, combination therapy was not cost-effective compared with nab-P alone.

Our analysis suggests that, from a US health care system perspective, toripalimab in combination with chemotherapy does not demonstrate a significant cost-effective advantage over nab-P chemotherapy as a first-line treatment for patients with TNBC at a WTP threshold of $100,000/QALY and has a limited impact on US health care policy and clinical practice.

Thyroid cancer (THCA) is the most prevalent endocrine tumor, and its incidence continues to increase every year. However, the processes underlying the aggressive progression of thyroid cancer are unknown. We concentrated on the prognostic and biological importance of thyroid cancer cuproptosis-related genes in this investigation. Genomic and clinical data were obtained from the UCSC XENA website, and cuproptosis-related genes were obtained from the FerrDb website. We performed differential expression analysis and Cox regression analysis to identify possible predictive targets associated with thyroid cancer prognosis. To assess the role of CDKN2A in thyroid cancer and the ability to predict prognosis on the basis of the CDKN2A expression level, we performed immunohistochemical staining, survival analysis, immunological analysis, functional analysis, and clinical analysis with respect to CDKN2A gene expression. CDKN2A expression levels were found to be inversely correlated with thyroid cancer prognosis. Higher levels of CDKN2A expression were associated with higher T, N, and clinicopathological stage and more residual tumor cells. Through univariate and multivariate Cox regression analyses, the CDKN2A expression level was shown to be linked with thyroid cancer patients' overall survival (OS). Moreover, we discovered that CDKN2A expression was linked to a dysfunctional tumor immune microenvironment. The study shows that CDKN2A, a cuproptosis-related gene, can be used as a prognostic marker for thyroid cancer.

To quantitatively investigate the pathological subtypes of lacrimal gland adenoid cystic carcinoma (LGACCs), the tumor immune microenvironment in each pathological subtype, and the relation to survival.

In this retrospective study, the tumor subtype was determined by H&E staining. Multiplex immunochemistry was performed to define specific immune cells. The tumor immune microenvironment (TIME) was sketched by sequential image scanning and reconstructed by a cytometry platform.

Eighteen patients with adequate paraffin blocks diagnosed with LGACC from 2012 to 2021 were included in this study. Thirteen patients out of the eighteen patients (72.2%)showed a mixture of different pathological subtypes. Each pathological subtype took different percentages on different tumors. The cribriform was the most common subtype, taking an overall percentage of 39%. The rest of the pathological subtypes were tubular (19%), basaloid (17%), cribriform and tubular mixture (C + T) 14%. The sclerosing and comedocarcinomic subtypes were the least seen in LGACC, taking a percentage of 11% altogether. Patients with cribriform dominant component had better overall survival than the non-cribriform dominant patients. Patients with basaloid dominant component had worse clinical outcomes than the non-basaloid dominant ones. The TIME showed high immunogenicity in the tumor margin but declined in the tumor areas. Pathological subtypes rather than individual differences determined the TIME phenotype. The cribriform subtype possessed more immune cell infiltration than other pathological subtypes.

LGACC is composed of multiple pathological subtypes. Each pathological subtype takes different percentages on different tumors, which is related to the prognosis. TIME pattern in LGACC varies among different pathological subtypes, which could indicate novel strategies in immunotherapy.

Breast cancer (BC) is one of the most common malignant tumors among women, accounting for 24.5% of all cancer cases and leading to 15.5% of cancer-related mortality. The treatment of BC patients remains a significant challenge due to the disease's high invasiveness, elevated metastatic potential, substantial drug resistance, and high recurrence rate. Exosomes, which are lipid-bilayer extracellular vesicles ranging in size from 30 to 150 nm, mediate intercellular communication between tumor cells and surrounding cells in the tumor microenvironment by transferring various bioactive substances, such as proteins, lipids, and nucleic acids. Recently, growing evidence has demonstrated that non-coding RNAs (ncRNAs) are enriched in exosomes and play a critical role in regulating cell proliferation, metastasis, drug resistance, and angiogenesis in BC. Consequently, exosomal ncRNAs have emerged as a promising therapeutic target for BC treatment, given their involvement in multiple processes of cancer progression. This review provides a comprehensive and in-depth analysis of emerging exosomal ncRNAs in BC, highlighting their potential biological mechanisms and advanced applications in BC treatment.

Oral cancer, a prevalent form of head and neck malignancy, accounts for 4% of global cancer cases. The most common type, oral squamous cell carcinoma (OSCC), has a survival rate of about 50%. Even though emerging molecular therapies show promise for managing oral cancer, current treatments like surgery, radiotherapy, and chemotherapy have significant side effects. In addition, the complex tumor microenvironment (TME), involving the extracellular matrix (ECM) and cells like fibroblasts and stromal cells like immune cells, promotes tumor growth and inhibits immune responses, complicating treatment. Nonetheless, immunotherapy is crucial in cancer treatment, especially in oral cancers. Indeed, its effectiveness lies in targeting immune checkpoints such as PD-1 and CTLA-4 inhibitors, as well as monoclonal antibodies like pembrolizumab and cetuximab, adoptive cell transfer methods (including CAR-T cell therapy), cytokine therapy such as IL-2, and tumor vaccines. Thus, these interventions collectively regulate tumor proliferation and metastasis by targeting the TME through autocrine-paracrine signaling pathways. Immunotherapy indeed aims to stimulate the immune system, leveraging both innate and adaptive immunity to counteract cancer cell signals and promote tumor destruction. This review will explore how the TME controls tumor proliferation and metastasis via autocrine-paracrine signaling pathways. It will then detail the effectiveness of immunotherapy in oral cancers, focusing on immune checkpoints, targeted monoclonal antibodies, adoptive cell transfer, cytokine therapy, and tumor vaccines.

Lung cancer remains one of the most widespread and deadliest malignant tumors globally, with a particularly high mortality rate among all cancers. Recently, immunotherapy, particularly immune checkpoint inhibitors (ICIs), has emerged as a crucial treatment strategy for lung cancer patients, following surgical intervention, radiotherapy, chemotherapy, and targeted drug therapies. However, the therapeutic limitations are caused owing to their low response rate and undesirable side effects such as immune-related pneumonitis. Therefore, developing new strategies to improve the efficacy of ICIs while minimizing immune-related adverse events will be crucial for cancer immunotherapy. The tumor immune microenvironment plays a significant role in the success of lung cancer immunotherapy, and the immunosuppressive characteristics of the immune microenvironment are one of the major obstacles to the poor immunotherapeutic effect. Phytochemicals, naturally occurring compounds in plants, have shown promise in enhancing cancer immunotherapy by remodeling the immunosuppressive microenvironment, offering the potential to increase the efficacy of ICIs. Therefore, this review summarizes the associated mechanisms of phytochemicals remodeling the immunosuppressive microenvironment in lung cancer. Additionally, the review will focus on the synergistic effects of combining phytochemicals with ICIs, aiming to improve anticancer efficacy and reduce side effects, which may hopefully offer novel strategies to overcome current limitations in immunotherapy.

Recent years, immunotherapy has emerged as a pivotal approach in cancer treatment. However, the response of gastric cancer to immunotherapy exhibits significant heterogeneity. Therefore, the early identification of gastric cancer patients who are likely to benefit from immunotherapy and the discovery of novel therapeutic targets are of critical importance.

We collected data from European Nucleotide Archive (ENA) and Gene Expression Omnibus (GEO) databases. In project PRJEB25780, we performed WGCNA analysis and Lasso regression and chose CXCR2P1 for the subsequent analysis. Then, we compared the expression difference of CXCR2P1 among different groups. Kaplan-Meier curve was used to analyze the prognostic value of CXCR2P1, which was validated by project IMvigor210 and GEO datasets. ESTIMATE and CIBERSORT algorithm were used to evaluate the reshaping effect of CXCR2P1 to immune microenvironment of tumor. Differentially expressed genes (DEG) analysis, enrichGO analysis, Gene Set Enrichment Analysis (GSEA) and co-expression analysis were used to explore the cell biological function and signaling pathway involved in CXCR2P1.

WGCNA identified CXCR2P1 as a hub gene significantly associated with immune response to PD-1 inhibitors in gastric cancer. CXCR2P1 expression was elevated in responders and correlated with better prognosis. Functional analysis revealed its role in reshaping the tumor immune microenvironment by promoting immune cell infiltration, including M1 macrophages, activated CD4+ T cells, and follicular helper T cells. CXCR2P1 enhanced antigen presentation via the MHC-II complex, influenced key immune pathways, such as Toll-like receptor signaling and T-cell activation, which led to the up-regulation of expression of PD-L1. GSEA showed CXCR2P1 were correlated with microRNAs. Through DEG analysis and expression analysis, MIR215 was identified as a potential direct target of CXCR2P1.

High expression of CXCR2P1 is correlated with better response to PD-1 inhibitor. It reshapes the immune microenvironment by increasing immune infiltration and changing the fraction of immune cells. In tumor immune microenvironment, CXCR2P1 can promote inflammation, enhance antigen presentation and activate the PD-1/PD-L1-related signaling pathway, which might be achieved by CXCR2P1-MIR215 axis.

The development of immune checkpoint inhibitors has revolutionized the treatment of patients with cancer. Targeting the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1(PD-L1) interaction using monoclonal antibodies has emerged as a prominent focus in tumor therapy with rapid advancements. However, the efficacy of anti-PD-1/PD-L1 treatment is hindered by primary or acquired resistance, limiting the effectiveness of single-drug approaches. Moreover, combining PD-1/PD-L1 with other immune drugs, targeted therapies, or chemotherapy significantly enhances response rates while exacerbating adverse reactions. Multispecific antibodies, capable of binding to different epitopes, offer improved antitumor efficacy while reducing drug-related side effects, serving as a promising therapeutic approach in cancer treatment. Several bispecific antibodies (bsAbs) targeting PD-1/PD-L1 have received regulatory approval, and many more are currently in clinical development. Additionally, tri-specific antibodies (TsAbs) and tetra-specific antibodies (TetraMabs) are under development. This review comprehensively explores the fundamental structure, preclinical principles, clinical trial progress, and challenges associated with bsAbs targeting PD-1/PD-L1.

CD161, encoded by the killer cell lectin-like receptor B1 (KLRB1) gene, exhibits varied roles among different tumors. This study aimed to explore both the potential value of CD161 as a prognostic biomarker for hepatocellular carcinoma (HCC) and its association with immune cell infiltration.

A total of 109 HCC patients who underwent surgery were retrospectively analyzed. Immunohistochemistry, bioinformatic analyses, and statistical measurements were used to investigate the associations between CD161 expression, immune cell infiltration, and clinical outcomes in both public databases and in-house cohorts.

CD161 was highly expressed at both protein and mRNA levels in adjacent normal tissues compared to tumor tissues of HCC patients. Meanwhile, CD161 was enriched in HCC cases characterized by smaller tumor sizes (≤5 cm) and the absence of portal vein tumor thrombus. Individuals with high CD161 expression showed extended overall survival (OS) and relapse free survival (RFS) compared to those with lower CD161 levels. CD161 was identified as an independent prognostic indicator for both OS and RFS. In addition, the enrichment analysis indicated a close correlation between CD161 and immune response, as well as between CD161 and the signaling pathways of cytokines and chemokines, implying its role in immune regulation during cancer development. Specifically, CD161 expression was positively associated with immunomodulators and tumor-infiltrating immune cells, especially CD8+T cells, CD4+T cells, and dendritic cells. Multiple public databases showed that patients with high CD161 expression were more likely to derive benefits from immunotherapy.

CD161 was identified as a promising prognostic biomarker for HCC, as its expression indicates a favorable prognosis. Additionally, CD161 is closely linked to high infiltration of immune cells, participates in the regulation of the tumor immune microenvironment, and holds promise as a potential biomarker for predicting the efficacy of immunotherapy.

Medicinal mushrooms have become increasingly important in the pharmaceutical industry because they contain a wealth of bioactive compounds and offer various nutritional benefits. These qualities also contribute to their widespread use in cooking. Global mycologists have suggested that a deeper understanding of mushrooms can aid in treating a variety of cancers at different stages. The excellent anticancer potential of fungi has inevitably attracted the attention of researchers, given the ever-increasing number of cases of lung cancer. Thus, the purpose of this review was to compile and synthesize the existing scientific literature about the potential of mushroom extracts particularly towards lung cancer prevention. A comprehensive literature search was conducted in electronic databases to identify relevant studies for the review. We found that 26 distinct kinds of mushrooms, prepared in over 10 different solvents, were used to make extracts that decreased the viability of different types of lung cancer cells (A549, NCI-H460, 3LL, H1264 cells etc.). We also examined a range of experimental models, including cell cultures (in vitro), mouse models (in vivo), as well as case studies and randomized controlled trials. The investigated mushrooms' effective mechanisms included: a reduction in the growth of cancer cells; an imbalanced percentage of cells in different phases of the cell cycle; an increase in autophagy and phagocytosis; an enhanced immune response; and the induction of cell apoptosis through the upregulation of pro-apoptotic factors and the downregulation of anti-apoptotic genes. Considering that mushrooms are consumed as a daily supplement, their potent pro-apoptotic properties and high antiproliferative efficacy are advantageous and could provide a model for further studies in this field as well as novel drug therapies and cancer treatments.

Cancer immunotherapy has shown promising results in the clinic, but it faces great challenges such as low response rates and low efficacy in solid tumors. c-Rel, a member of the nuclear factor (NF)-κB family, is a newly described immune checkpoint for myeloid-derived suppressor cells (MDSCs), which contribute to the formation of immune-suppressive tumor microenvironment and resistance to cancer immunotherapy. How to selectively target myeloid c-Rel for the treatment of cancer is not well established. In this study, we investigated the feasibility and efficacy of knocking down myeloid c-Rel with siRNA-loaded peptide-based nanoparticles as a new cancer immunotherapy strategy.

The knockdown of c-Rel gene by the siRNA-loaded peptide nanoparticles was confirmed on MDSCs in vitro and in vivo. The effects of c-Rel silencing on cell number and immune suppressive function of the murine bone marrow-derived MDSCs were then investigated. To evaluate the anti-tumor efficacy of the c-Rel siRNA loaded nanoparticles, female C57BL/6 mice with subcutaneous B16 tumor were treated with PBS, c-Rel siRNA loaded nanoparticles, control siRNA loaded nanoparticles or empty nanoparticles. The tumor growth and body weight of mice were monitored, and the numbers and immune activities of tumor infiltrated immune cells in different groups were analyzed at the end of the experiment. The immune function of MDSCs isolated from tumor bearing mice received different treatments were further investigated ex vivo by T cell proliferation assays.

The c-Rel siRNA nanoparticles significantly reduced c-Rel expression in MDSCs, diminished both the number and immune suppressive function of MDSCs, and enhanced intratumor CD8+ T cell responses. Significantly reduced tumor growth was observed in mice treated with the c-Rel siRNA nanoparticles compared to control mice.

Our data indicates that peptide-based nanoparticles can be successfully utilized to target the myeloid immune checkpoint c-Rel for the treatment of cancer.

Cervical adenocarcinoma (ADC) is more aggressive compared to other types of cervical cancer (CC), such as squamous cell carcinoma (SCC). The tumor immune microenvironment (TIME) and tumor heterogeneity are recognized as pivotal factors in cancer progression and therapy. However, the disparities in TIME and heterogeneity between ADC and SCC are poorly understood.

We performed single-cell RNA sequencing on 11 samples of ADC tumor tissues, with other 4 SCC samples served as controls. The immunochemistry and multiplexed immunofluorescence were conducted to validate our findings.

Compared to SCC, ADC exhibited unique enrichments in several sub-clusters of epithelial cells with elevated stemness and hyper-malignant features, including the Epi_10_CYSTM1 cluster. ADC displayed a highly immunosuppressive environment characterized by the enrichment of regulatory T cells (Tregs) and tumor-promoting neutrophils. The Epi_10_CYSTM1 cluster recruits Tregs via ALCAM-CD6 signaling, while Tregs reciprocally induce stemness in the Epi_10_CYSTM1 cluster through TGFβ signaling. Importantly, our study revealed that the Epi_10_CYSTM1 cluster could serve as a valuable predictor of lymph node metastasis for CC patients.

This study highlights the significance of ADC-specific cell clusters in establishing a highly immunosuppressive microenvironment, ultimately contributing to the heightened aggressiveness and poorer prognosis of ADC compared to SCC.

Funded by the National Natural Science Foundation of China (82002753; 82072882; 81500475) and the Natural Science Foundation of Hunan Province (2021JJ40324; 2022JJ70103).

Immunotherapy is becoming a promising strategy for treating diverse cancers. However, it benefits only a selected group of gastric cancer (GC) patients since they have highly heterogeneous immunosuppressive microenvironments. Thus, a more sophisticated immunological subclassification and characterization of GC patients is of great practical significance for mRNA vaccine therapy. This study aimed to find a new immunological subclassification for GC and further identify specific tumor antigens for mRNA vaccine development. First, deep autoencoder (AE)-based clustering was utilized to construct the immunological profile and to uncover four distinct immune subtypes of GC, labeled as Subtypes 1, 2, 3, and 4. Then, in silico prediction using machine learning methods was performed for accurate discrimination of new classifications with an average accuracy of 97.6%. Our results suggested significant clinicopathology, molecular, and immune differences across the four subtypes. Notably, Subtype 4 was characterized by poor prognosis, reduced tumor purity, and enhanced immune cell infiltration and activity; thus, tumor-specific antigens associated with Subtype 4 were identified, and a customized mRNA vaccine was developed using immunoinformatic tools. Finally, the influence of the tumor microenvironment (TME) on treatment efficacy was assessed, emphasizing that specific patients may benefit more from this therapeutic approach. Overall, our findings could help to provide new insights into improving the prognosis and immunotherapy of GC patients.

Gene therapy, epigenetic therapies, natural compounds targeted therapy, photodynamic therapy, nanoparticles, and precision medicines are becoming available to diagnose and treat cancer. Gracillin, a natural steroidal saponin extracted from herbs, has shown potent efficacy against a range of malignancies. In this study, we investigated the molecular anticancer mechanisms of gracillin. We showed that gracillin dose-dependently suppressed proliferation, migration, and invasion in breast cancer, liver cancer, and glioblastoma cells with IC50 values around 1 μM, which were associated with MST-independent activation of Hippo signaling pathway and subsequent decreased YAP activity. We demonstrated that gracillin activated the Hippo signaling by inducing Merlin/LATS protein-protein interaction (PPI). A competitive inhibitory peptide (SP) derived from the binding interface of the PPI, disrupted the interaction, abolishing the anticancer activity of gracillin. In nude mice bearing MDA-MB-231, HCCLM3, or U87MG xenograft tumor, administration of gracillin (5, 10 mg·kg-1·d-1, i.g. for 21 days) dose-dependently suppressed the tumor growth, associated with the induced Merlin/LATS PPI, activated Hippo signaling, as well as decreased YAP activity in tumor tissues. Our data demonstrate that gracillin is an efficacious therapeutic agent for cancer treatment, induction of Merlin/LATS PPI might provide proof-of-concept in developing therapeutic agent for cancer treatment.

NUP62, a key component of the nuclear pore complex, is closely associated with cellular functions and cancer progression. However, its expression patterns, prognostic value, and relationship with tumour immunity and drug sensitivity across multiple cancers have not been systematically studied. This study used multi-omics analyses combined with experimental validation in gastric cancer to investigate the expression, functional characteristics, and clinical relevance of NUP62 in cancer.

Data from TCGA, GTEx, and CPTAC databases were used to analyse the expression, mutation characteristics, and clinical associations of NUP62. Tools such as SangerBox, TIMER 2.0, and GSEA were employed to evaluate the relationship between NUP62 and the tumour immune microenvironment, as well as its involvement in signalling pathways. Immunohistochemistry and RT-PCR were used to validate the expression of NUP62 in gastric cancer tissues. PRISM and CTRP databases were utilised to assess the correlation between NUP62 expression and drug sensitivity.

NUP62 was significantly upregulated in multiple cancers and was associated with poor prognosis in cancers such as clear cell renal carcinoma (KIRC), lower-grade glioma (LGG), and adrenocortical carcinoma (ACC), while playing a protective role in others, such as bladder cancer (BLCA) and stomach cancer (STAD). Functional analyses showed that NUP62 is involved in cell cycle regulation, DNA damage repair, and tumour immunity. High NUP62 expression was significantly correlated with increased infiltration of immune cells, such as macrophages and T cells, and a higher response rate to immunotherapy. Drug sensitivity analysis identified NUP62 as a marker of sensitivity to various chemotherapeutic agents. Validation experiments demonstrated that NUP62 mRNA and protein levels were significantly higher in gastric cancer tissues than in adjacent normal tissues.

NUP62 plays a critical role in multiple cancers and shows potential as a biomarker for cancer diagnosis, prognosis, and therapeutic response prediction. Its role in tumour immunity and signalling pathways highlights its potential as a target for immunotherapy and precision medicine.

tsRNA is a class of non-coding RNAs derived from mature or precursor tRNAs. In recent years, more and more studies have explored the correlation between tsRNAs and tumours. tsRNAs can affect the biological behaviours of tumour cells such as proliferation, apoptosis and metastasis by regulating gene expression, protein translation or post-transcriptional regulation. In this paper, we systematically review the production, biological function and research progress of tsRNA in tumour and discuss its prospects as biomarkers and therapeutic targets.

In recent years, numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment (TIME). However, to date, no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric methods.

To describe the current global research status on the correlation between gut microbiota and the TIME, and to identify the most influential countries, research institutions, researchers, and research hotspots related to this topic.

We searched for all literature related to gut microbiota and TIME published from January 1, 2014, to May 28, 2024, in the Web of Science Core Collection database. We then conducted a bibliometric analysis and created visual maps of the published literature on countries, institutions, authors, keywords, references, etc., using CiteSpace (6.2R6), VOSviewer (1.6.20), and bibliometrics (based on R 4.3.2).

In total, 491 documents were included, with a rapid increase in the number of publications starting in 2019. The country with the highest number of publications was China, followed by the United States. Germany has the highest number of citations in literature. From a centrality perspective, the United States has the highest influence in this field. The institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang University. However, the institution with the most citations was the United States National Cancer Institute. Among authors, Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this field. The most cited author was Fan XZ. The results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology, Cancers, and Frontiers in Oncology. The three most frequently used keywords were gut microbiota, tumor microenvironment, and immunotherapy.

This study systematically elaborates on the research progress related to gut microbiota and TIME over the past decade. Research results indicate that the number of publications has rapidly increased since 2019, with research hotspots including "gut microbiota", "tumor microenvironment" and "immunotherapy". Exploring the effects of specific gut microbiota or derived metabolites on the behavior of immune cells in the TIME, regulating the secretion of immune molecules, and influencing immunotherapy are research hotspots and future research directions.

Gastric cancer is one of the most frequent malignancies and a serious concern in the global public health realm. Neutrophils, the most numerous myeloid cells in human blood, are emerging as significant regulatory variables in cancer. This study examines the molecular processes behind the link between gastric cancer's malignant character and neutrophils in the disease. This study aims to reveal the role of P2RX1 in neutrophils in gastric cancer and investigate its effects on the migration, invasion, and apoptosis of gastric cancer cells, with the hope of providing new targets and strategies for the treatment of gastric cancer. P2RX1 expression levels in gastric cancer samples were examined using The Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD). The signal pathways enriched by P2RX1-related differential gene expression were examined using GSEA. P2RX1 mRNA levels were examined using qPCR. Jak/Stat signaling pathway-related proteins and P2RX1 expression levels were subjected to western blot analysis. The apoptotic rate, migration, invasion, and cell viability were evaluated using flow cytometry, Transwell, and CCK-8 tests. Immunohistochemistry was used to detect the expression of P2RX1 in tumor tissues. Neutrophils and P2RX1 were both underexpressed in gastric cancer. In gastric cancer neutrophils, overexpression of P2RX1 increased cancer cell apoptosis while suppressing migration, invasion, and viability of the cells. Jak/Stat signaling pathway was connected to production of neutrophil P2RX1, and P2RX1 overexpression could trigger the pathway in vivo and in vitro. By activating its own Jak/Stat signaling pathway, overexpression of P2RX1 in gastric cancer neutrophils improved neutrophil survival, which in turn suppressed the migration, invasion, and viability of gastric cancer cells and raised their apoptosis rate. This suggests that P2RX1 may play a significant anti-tumor role in the tumor microenvironment of gastric cancer, indicating its value as a potential therapeutic target.

N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, plays a critical role in the development and progression of various diseases, including cancer, through its regulation of RNA degradation, stabilization, splicing, and cap-independent translation. Emerging evidence underscores the significant role of m6A modifications in both pro-tumorigenic and anti-tumorigenic immune responses. In this review, we provide a comprehensive overview of m6A modifications and examine the relationship between m6A regulators and cancer immune responses. Additionally, we summarize recent advances in understanding how m6A modifications influence tumor immune responses by directly modulating immune cells (e.g., dendritic cells, tumor-associated macrophages, and T cells) and indirectly affecting cancer cells via mechanisms such as cytokine and chemokine regulation, modulation of cell surface molecules, and metabolic reprogramming. Furthermore, we explore the potential synergistic effects of targeting m6A regulators in combination with immune checkpoint inhibitor (ICI) therapies. Together, this review consolidates current knowledge on the role of m6A-mediated regulation in tumor immunity, offering insights into how a deeper understanding of these modifications may identify patients who are most likely to benefit from immunotherapies.

Histone deacetylase 3 (HDAC3) has emerged as a critical epigenetic regulator in tumor progression and immune modulation, positioning it as a promising target for enhancing cancer immunotherapy. This work comprehensively explores HDAC3's multifaceted roles, focusing on its regulation of key immune-modulatory pathways such as cGAS-STING, ferroptosis, and the Nrf2/HO-1 axis. These pathways are central to tumor immune evasion, antigen presentation, and immune cell activation. Additionally, the distinct effects of HDAC3 on various immune cell types-including its role in enhancing T cell activation, restoring NK cell cytotoxicity, promoting dendritic cell maturation, and modulating macrophage polarization-are thoroughly examined. These findings underscore HDAC3's capacity to reshape the tumor immune microenvironment, converting immunologically "cold tumors" into "hot tumors" and thereby increasing their responsiveness to immunotherapy. The therapeutic potential of HDAC3 inhibitors is highlighted, both as standalone agents and in combination with immune checkpoint inhibitors, to overcome resistance and improve treatment efficacy. Innovative strategies, such as the development of selective HDAC3 inhibitors, advanced nano-delivery systems, and integration with photodynamic or photothermal therapies, are proposed to enhance treatment precision and minimize toxicity. By addressing challenges such as toxicity, patient heterogeneity, and resistance mechanisms, this study provides a forward-looking perspective on the clinical application of HDAC3 inhibitors. It highlights its significant potential in personalized cancer immunotherapy, paving the way for more effective treatments and improved outcomes for cancer patients.

NALCN has been identified as a tumor suppressor gene, and its role in human cancer progression has garnered significant attention. However, there is a paucity of experimental studies specifically addressing the relationship between NALCN and immune cell infiltration in gastric cancer (GC).

The expression levels of NALCN in tumor tissues, peripheral blood and gastric cancer cells lines from patients with GC were assessed using RNA sequencing, immunohistochemistry (IHC) staining and RT-qPCR. Data obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were utilized to investigate the correlation between NALCN expression and immune cell infiltration in GC. Subsequently, the relationship between NALCN expression and infiltrating immune cells in GC tissues was examined through immunofluorescence method. Additionally, in vitro experiments were conducted to evaluate the impact of NALCN knockdown on T cells function in GC cell lines.

RNA sequencing analysis revealed that NALCN expression was significantly downregulated in GC tissues. Specifically, NALCN levels were lower in GC tumor tissues and plasma compared to adjacent non-tumor tissues and healthy controls. Consistent with these findings, the expression trend of NALCN mRNA in the GEO database mirrored the experimental results. Mechanistically, NALCN knockdown markedly enhanced cell proliferation, colony formation and migration while reducing apoptosis rates in AGS and GES-1 cells. Analysis of the TCGA database indicated a positive correlation between NALCN expression and the infiltration of B cells, cytotoxic cells, immature dendritic cells (iDC) cells, CD8+ T cells, and others in GC tissue. Conversely, Th17 and Th2 cells infiltration exhibited a negative correlation with NALCN expression. Immunofluorescence staining confirmed that B cells and CD8 T cells were more abundant in GC tumor tissues with high NALCN expression, whereas Th17 and Th2 cells were less prevalent. Subsequently, we co-cultured GC cells transfected with NALCN knockdown or control vectors along with their supernatants with T cells. The results demonstrated that NALCN knockdown in GC cells or their supernatants inhibited T cell proliferation compared to control conditions. Moreover, NALCN may play a role in glucose and glutamine uptake.

NALCN facilitates immune cell aggregation in GC and has potential as a biomarker for immune infiltration.

Tumor development involves the critical role of programmed cell death (PCD), but the correlation between colon adenocarcinoma (COAD) and PCD-related genes is not clear.

Subtyping analysis of COAD was performed by consensus clustering based on The Cancer Genome Atlas (TCGA), with the AC-ICAM queue from the cBioportal database as a validation set. Immune infiltration of the samples was evaluated using CIBERSORT and Microenvironment Cell Populations (MCP)-counter algorithms. Patients' immunotherapy response was predicted by the TIDE and aneuploidy scores. Pathway enrichment analysis was conducted with gene set enrichment analysis (GSEA). A RiskScore model was established with independent prognostic PCD-related genes filtered by Cox regression analysis. The mafCompare function was used to compare the differences in mutation rates of somatic genes. Wound healing, transwell assays and Flow cytometer were applied to measure the cell migration, invasion and apoptosis.

The patients were grouped into S1 and S2 subtypes based on a total of 21 PCD genes associated with the prognostic outcomes of COAD. Specifically, patients of S1 subtype were mainly related to the pathway activation in tumor invasion and deterioration and had a worse prognosis. A RiskScore model was established based on six prognostic genes, including two protective genes (ATOH1, ZG16) and four risk genes (HSPA1A, SEMA4C, CDKN2A, ARHGAP4). Notably, silencing of CDKN2A inhibited the activity of migration and invasion and promoted apoptosis of tumor cells. Based on the RiskScore model, the patients were grouped into high- and low-risk groups. Independent prognostic factors, namely, Age, pathologic_M, pathologic_stage, and RiskScore, were integrated to develop a nomogram with strong good prediction performance. High-risk group had high-expressed immune checkpoint genes and higher TIDE scores, showing a strong immune escape ability and less active immunotherapy response. Compared to the low-risk group, TP53 exhibited a higher rate of somatic mutation in the high-risk group.

We constructed a RiskScore model with six PCD-related genes for the prognostic assessment of COAD, providing a valuable insight into the exploration of new targets for the prognostic improvement in COAD.

Osteosarcoma (OS) is a commonly observed malignant tumor in orthopedics that has a very poor prognosis. The endosomal sorting complex required for transport (ESCRT) is important for the development and progression of cancer and may be a significant target for cancer therapy. First, we built a prognostic signature using 7 ESCRT-related genes (ERGs) to predict OS patient prognosis. Analysis of internal and external datasets revealed that the ERG signature has good predictive ability and reproducibility. Immune analysis demonstrated a significant correlation between OS patient immune status and ERG signature score. Moreover, ERG signature score was found to be associated with the response of OS patients to immunotherapy and anticancer drugs. Additionally, we constructed a prognostic signature consisting of 10 ESCRT-related long noncoding RNAs (ERLs) that effectively predicted the prognosis of OS patients. Furthermore, two subgroups of OS patients with distinct prognoses (clusters 1 and 2) were identified. Finally, LMO7-AS1 was chosen for functional experimental validation. The knockdown of LMO7-AS1 suppressed the malignant progression of OS cells. Furthermore, transcriptome sequencing was performed on OS cells and revealed a correlation between LMO7-AS1 and the PI3K-Akt signaling pathway. In conclusion, our ESCRT transcriptome-associated signatures can act as prognostic biomarkers for OS, and LMO7-AS1 is a novel therapeutic target for the treatment of OS.

Cancer remains a formidable global health challenge, necessitating innovative therapeutic approaches to enhance treatment efficacy and reduce adverse effects. The traditional Chinese medicine (TCM), as an embodiment of ancient wisdom, has been validated to regulate the holistic human capacity against both internal and external "evils" in accordance with TCM principles. Therefore, it stands to reason to integrate TCM into current cancer therapy paradigms, such as chemotherapy, immunotherapy, and targeted therapy. This strategy conceptually intends to circumvent the inevitable side effects derived from present treatment, alleviate the discomfort, mollify the detrimental mood and synergize tumoricidal effects of distinct approaches. However, it is still vague whether TCM exert favorable function in cancer treatment. Therefore, it is imperative to retrieve and compile the existing literature on TCM in the realm of cancer, followed by a comprehensive recapitulation and synthesis of its core findings. Recently, with the advancement of contemporary biologic and medical theory and technology, it has become both feasible and imperative to elucidate the molecular signaling mechanisms and cellular biology underlying TCM. Specifically, leveraging TCM pharmaceutic components can not only directly impact tumor biology at the molecular level, but regulate the tumor immune environment through distinct pathways. Additionally, the administration of external TCM treatments such as acupuncture and moxibustion also demonstrates beneficial effects in cancer patients. Through comprehensive analysis, we demonstrated that TCM not only potentially increases the efficacy of conventional cancer treatments, but also significantly mitigates their toxic side effects, thereby prolonging patients' prognosis and improving their living quality. Furthermore, we have underscored the challenges and prospects associated with the integration of TCM into contemporary oncological practices, placing particular emphasis on the imperative for rigorous clinical trials and molecular investigations to substantiate the efficacy and safety of these combined therapeutic approaches. This synthesis aims to pave the way for a more integrated approach to cancer treatment rooted in both traditional wisdom and cutting-edge science.

This study delved into the molecular mechanisms underlying mechanical stress-induced intervertebral disc degeneration (msi-IDD) through single-cell and high-throughput transcriptome sequencing in mouse models and patient samples. Results exhibited an upsurge in macrophage presence in msi-IDD intervertebral disc (IVD) tissues, with secreted phosphoprotein 1 (SPP1) identified as a pivotal driver exacerbating degeneration via the protein kinase RNA-like endoplasmic reticulum kinase/ activating transcription factor 4/ interleukin-10 (PERK/ATF4/IL-10) signaling axis. Inhibition of SPP1 demonstrated promising outcomes in mitigating msi-IDD progression in both in vitro and in vivo models. These findings underscore the therapeutic promise associated with the modulation of the PERK signaling pathway in IDD, shedding light on the pathogenesis of msi-IDD and proposing a promising avenue for intervention strategies.

The rising incidence of breast cancer and its heterogeneity necessitate precise tools for predicting patient prognosis and tailoring personalized treatments. Epigenetic changes play a critical role in breast cancer progression and therapy responses, providing a foundation for prognostic model development.

We developed the Machine Learning-derived Epigenetic Model (MLEM) to identify prognostic epigenetic gene patterns in breast cancer. Using multi-cohort transcriptomic datasets, MLEM was constructed with rigorous machine learning techniques and validated across independent datasets. The model's performance was further corroborated through immunohistochemical validation on clinical samples.

MLEM effectively stratified breast cancer patients into high- and low-risk groups. Low-MLEM patients exhibited improved prognosis, characterized by enhanced immune cell infiltration and higher responsiveness to immunotherapy. High-MLEM patients showed poorer prognosis but were more responsive to chemotherapy, with vincristine identified as a promising therapeutic option. The model demonstrated robust performance across independent validation datasets.

MLEM is a powerful prognostic tool for predicting breast cancer outcomes and tailoring personalized treatments. By integrating epigenetic insights with machine learning, this model has the potential to improve clinical decision-making and optimize therapeutic strategies for breast cancer patients.

Colorectal cancer (CRC) is the third most prevalent malignancy and the second leading cause of cancer-related mortality worldwide, with an increasing shift towards younger age of onset. In recent years, there has been increasing recognition of the significance of tRNA-derived small RNAs (tsRNAs), encompassing tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs). Their involvement in regulating translation, gene expression, reverse transcription, and epigenetics has gradually come to light. Emerging research has revealed dysregulation of tsRNAs in CRC, implicating their role in CRC initiation and progression, and highlighting their potential in early diagnosis, prognosis, and therapeutic strategies. Although the clinical application of tsRNAs is still in its early stages, recent findings highlight a close relationship between the biogenesis and function of tsRNAs, tRNA chemical modifications, and the tumor immune microenvironment (TIME). Additionally, similar to other small RNAs, tsRNAs can be effectively delivered via nanoparticles (NPs). Consequently, future research should focus on elucidating the clinical significance of tsRNAs concerning base modifications, TIME regulation, cancer immunotherapy, and NPs delivery systems to facilitate their clinical translation.

RAC1, a member of the Rho family GTPases, has been implicated in various cancers, yet its pan-cancer landscape and role in the tumor immune microenvironment remain underexplored. This study presents a comprehensive analysis of RAC1 across 33 cancer types, revealing its high expression in a broad range of cancers and its association with poor prognosis. RAC1 expression correlates with genomic alterations, including CNVs, TMB, and MSI. RAC1 knockdown reduces cell proliferation and metastasis in breast and lung cancer cells, suggesting its oncogenic potential. Notably, RAC1 is negatively correlated with B cell infiltration, indicating its role in regulating the immune microenvironment. Functional enrichment analysis showed that high RAC1 expression is linked to lower enrichment in B cell activation and immune response pathways. Single-cell transcriptome analysis identified RAC1 expression primarily in epithelial cells, associated with tumor progression, and spatial transcriptome analysis showed a mutually exclusive co-localization between B cell infiltration regions and RAC1-expressing epithelial cells. Based on RAC1 expression and B cell interaction, a prognostic signature was established to predict prognosis at the pan-cancer level.

NFKB1, a core transcription factor critical in various biological process (BP), is increasingly studied for its role in tumors. This research combines literature reviews, meta-analyses, and bioinformatics to systematically explore NFKB1's involvement in tumor initiation and progression. A unique focus is placed on the NFKB1-94 ATTG promoter polymorphism, highlighting its association with cancer risk across diverse genetic models and ethnic groups, alongside comprehensive analysis of pan-cancer expression patterns and drug sensitivity. The study reveals the intricate connections between NFKB1 and tumors, highlighting its significant roles in invasion, metastasis, genomic stability, and metabolic changes. Through meta-analysis, it is evidenced that tumor specimens exhibit increased NFKB1 expression when compared to non-tumor specimens, although its association with cancer incidence requires further investigation. Analysis from the Gene Expression Omnibus (GEO) database suggests that high NFKB1 gene expression may not markedly impact tumor patient prognosis. The noticeable correlation between the NFKB1-94 ATTG promoter polymorphic sequence and elevated cancer susceptibility is highlighted across different genetic models. Furthermore, bioinformatics analysis uncovers NFKB1's association with the sensitivity to various anticancer drugs and its central involvement in crucial BP like the cell cycle, cytoskeleton assembly, and cellular senescence. Overall, NFKB1's expression and polymorphisms are significantly linked to tumor risk, prognosis, and treatment response, highlighting its prospect as a forthcoming aim for cancer treatment. This study offers a robust foundation for further exploration of NFKB1's mechanisms and the development of innovative therapeutic strategies.

Undifferentiated carcinoma (UC) is a rare subtype of pancreatic cancer distinguished from UC with osteoclast-like giant cells (UC-OGC) in 2019, affecting interpretation of literature that does not distinguish these subtypes. We sought to identify translationally relevant differences between these 2 variants and compared with pancreatic ductal adenocarcinoma.

We characterized clinical and multiomic differences between UC (n = 32) and UC-OGC (n = 15) using DNA sequencing, RNA sequencing, and multiplex immunofluorescence and compared these findings with pancreatic ductal adenocarcinoma.

Characteristics at diagnosis were similar between UC and UC-OGC, though the latter was more resectable (P = .009). Across all stages, median overall survival was shorter for UC than for UC-OGC (0.4 years vs 10.8 years, respectively; P = .003). This shorter survival was retained after stratification by resection, albeit without statistical significance (1.8 years vs 11.9 years, respectively; P = .08). In a subset of patients with available tissue, the genomic landscape was similar among UC (n = 9), UC-OGC (n = 5), and pancreatic ductal adenocarcinoma (n = 159). Bulk RNA sequencing was deconvoluted and, along with multiplex immunofluorescence in UC (n = 13), UC-OGC (n = 5), and pancreatic ductal adenocarcinoma (n = 16), demonstrated statistically significantly increased antigen-presenting cells, including M2 macrophages and natural killer cells, and decreased cytotoxic and regulatory T cells in UC and UC-OGC vs pancreatic ductal adenocarcinoma. Findings were similar between UC and UC-OGC , except for decreased regulatory T cells in UC-OGC (P = .04).

In this series, UC was more aggressive than UC-OGC, with these variants having more antigen-presenting cells and fewer regulatory T cells than pancreatic ductal adenocarcinoma, suggesting potential for immune-modulating therapies in the treatment of these pancreatic cancer subtypes.

Background: Killer Cell Lectin Like Receptor D1 (KLRD1) plays a crucial role in antitumor immunity. However, its expression patterns across various cancers, its relationship with patient prognosis, and its potential as an immunotherapy target remain inadequately understood. Methods: We analyzed KLRD1 expression across various cancer types using multi-omics data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases, correlating it with patient prognosis. Single-cell RNA sequencing data were employed to further explore KLRD1 expression in natural killer (NK) cells and exhausted CD8+ T cells (CD8Tex). Functional enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) identified the biological processes and pathways associated with KLRD1. Immune infiltration analysis, conducted via CIBERSORT, assessed the relationship between KLRD1 expression and immune cell infiltration within the tumor microenvironment. Furthermore, the Tracking Tumor Immunophenotype (TIP) meta-server and Easier tool were employed to assess the role of KLRD1 in the cancer immunity cycle and to predict immunotherapy responses. Drug sensitivity was predicted using tools like CellMiner and the Genomics of Drug Sensitivity in Cancer (GDSC) database to explore the link between KLRD1 expression and responsiveness to various anticancer drugs. Results: KLRD1 exhibits significant differential expression and strong prognostic value across cancers, particularly as an independent prognostic factor in head and neck squamous cell carcinoma (HNSC). Single-cell analysis revealed high expression of KLRD1 in NK and CD8Tex cells, indicating its critical role in antitumor immune responses. Functional enrichment analyses showed that KLRD1 is involved in several immune-related signaling pathways, including NK cell-mediated cytotoxicity and T cell receptor pathways. Immune infiltration analysis further confirmed a positive correlation between KLRD1 expression and the infiltration of various immune cells. Moreover, higher KLRD1 expression in HNSC is associated with enhanced immune pathway activity, increased sensitivity to cell division inhibitors, and the identification of arachidonyltrifluoromethane as a potential compound to counteract its oncogenic effects. Conclusion: In HNSC, KLRD1 is a key prognostic marker and potential target for personalized immunotherapy.

Tumor therapy has advanced significantly in recent years, but tumor cells can still evade and survive the treatment through various mechanisms. Notably, tumor cells use autophagy to sustain viability by removing impaired mitochondria and clearing excess reactive oxygen species (ROS). In this study, the aim is to amplify intracellular oxidative stress by inhibiting mitochondrial autophagic flux. Multisynergistic environmental-response nanoparticles (ERNs) are engineered by integrating gold nanoparticles and copper peroxide with borosilicate bioactive glass. The controlled release of copper and inhibition of autophagy flux triggered an overabundance and accumulation of oxidative stress within the tumor cells. This stress triggered immunogenic tumor cell death, believed to initiate a systemic immune response. The tumor microenvironment (TME) transitioned back to a normal physiological state as tumor cells are ablated. ERNs responded to the microenvironment changes by depositing hydroxyapatite on the surface and spontaneously enhancing bone regeneration. This innovative formulation facilitates the functional transition of ERNs from "anti-tumor therapy" to "biomineralization" that kills cancers and induces new bone formation. Overall, it is shown that the ERNs effectively eradicate cancers by utilizing chemodynamic therapy, starvation therapy, and immunotherapy.

This study aims to analyze Coronavirus Disease 2019 (COVID-19)-associated copper-death genes using the Gene Expression Omnibus (GEO) dataset and machine learning, exploring their immune microenvironment correlation and underlying mechanisms. Utilizing GEO, we analyzed the GSE217948 dataset with control samples. Differential expression analysis identified 16 differentially expressed copper-death genes, and Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) quantified immune cell infiltration. Gene classification yielded two copper-death clusters, with Weighted Gene Co-expression Network Analysis (WGCNA) identifying key module genes. Machine learning models (random forest, Support Vector Machine (SVM), Generalized Linear Model (GLM), eXtreme Gradient Boosting (XGBoost)) selected 6 feature genes validated by the GSE213313 dataset. Ferredoxin 1 (FDX1) emerged as the top gene, corroborated by Area Under the Curve (AUC) analysis. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) revealed enriched pathways in T cell receptor, natural killer cytotoxicity, and Peroxisome Proliferator-Activated Receptor (PPAR). We uncovered differentially expressed copper-death genes and immune infiltration differences, notably CD8 T cells and M0 macrophages. Clustering identified modules with potential implications for COVID-19. Machine learning models effectively predicted COVID-19 risk, with FDX1's pivotal role validated. FDX1's high expression was associated with immune pathways, suggesting its role in COVID-19 pathogenesis. This comprehensive approach elucidated COVID-19-related copper-death genes, their immune context, and risk prediction potential. FDX1's connection to immune pathways offers insights into COVID-19 mechanisms and therapy.

As the primary glial cells in the peripheral nervous system (PNS), Schwann cells (SCs) have been proven to influence the behavior of cancer cells profoundly and are involved in cancer progression through extensive interactions with cancer cells and other stromal cells. Indeed, the tumor microenvironment (TME) is a critical factor that can significantly limit the efficacy of immunotherapeutic approaches. The TME promotes tumor progression in part by reshaping an immunosuppressive state. The immunosuppressive TME is the result of the crosstalk between the tumor cells and the different immune cell subsets, including macrophages, natural killer (NK) cells, dendritic cells (DCs), lymphocytes, myeloid-derived suppressor cells (MDSCs), etc. They are closely related to the anti-tumor immune status and the clinical prognosis of cancer patients. Increasing research demonstrates that SCs influence these immune cells and reshape the formation of the immunosuppressive TME via the secretion of various cytokines, chemokines, and other effector molecules, eventually facilitating immune evasion and tumor progression. In this review, we summarize the SC reprogramming in TME, the emerging role of SCs in tumor immune microenvironment, and the underlying mechanisms involved. We also discuss the possible therapeutic strategies to selectively target SCs, providing insights and perspectives for future research and clinical studies involving SC-targeted treatment.

Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1) encodes a core protein that has a crucial function in the metabolism of cholesterol and lipids. This transcription factor is a member of the family of transcription factors and highly expressed in a variety of cancer types. As of now, there are few reports on the relationship between the expression of SREBF1 and colon adenocarcinoma (COAD). Hence, this study utilizes databases and a range of experiments to explore the relationship between the expression of SREBF1 and tumor immune infiltration, as well as the occurrence and development of tumors.

The expression of SREBF1 in pan-cancers was retrieved through databases such as TIMER, Gene Expression Profiling Interactive Analysis (GEPIA), and UALCAN. The expression of SREBF1 in HCT-116 and SW480 cells was detected using western blot. Furthermore, we also found that knockdown SREBF1 can inhibit the proliferation and migration of COAD cells. The correlation between SREBF1 and autophagy in COAD cells was detected using acridine orange (AO) staining, western blot, and immunofluorescence (IF).

The databases of TIMER, GEPIA and UALCAN revealed that SREBF1 is overexpressed in pan-cancer tissues, and closely associated with the prognosis of the patients with cancer. Further immunohistochemical staining showed that SREBF1 was overexpressed in COAD, and closely related to the clinical stage and lymph node metastasis. Western blot revealed that SREBF1 was significantly expressed in both HCT-116 and SW480 COAD cells; knockdown of SREBF1 could inhibit the proliferation, DNA replication, and migration of COAD cells. The AO staining, western blot, and IF experiments also showed that silencing SREBF1 could promote the autophagy of COAD cell. Meanwhile, the TIMER database indicates a significant positive correlation between the presence of immune cells in COAD and variations in copy number alteration of SREBF1.

SREBF1 might serve as a potential prognostic marker for COAD and be associated with immune cell infiltration.

Disulfidptosis has recently emerged as a novel form of regulated cell death (RCD). Evasion of cell death is a hallmark of cancer, and the resistance of many tumors to apoptosis-inducing therapies has heightened interest in exploring alternative RCD mechanisms.

Transcriptomic and clinical data were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA). Glioma samples were classified using non-negative matrix factorization (NMF). A predictive model was constructed using Lasso regression analysis, and its performance was evaluated through receiver operating characteristic (ROC) and Kaplan-Meier survival analyses. The relationship between the model and the tumor immune microenvironment (TIME) as well as treatment sensitivity was also assessed. Finally, we validated the expression of key signature genes in glioma.

Glioma samples were categorized into two distinct subtypes based on disulfidptosis-related genes, showing significant differences in overall survival (OS) and progression-free survival (PFS) between the subtypes. A genetic risk score model was then developed using these genes. A nomogram predicting OS was constructed using the risk score and clinical variables. Patients were stratified into low- and high-risk groups based on the median risk score from the TCGA cohort. Low-risk patients had significantly better outcomes compared to high-risk patients (TCGA cohort, OS: p < 0.001; PFS: p < 0.001; CGGA cohort, OS: p < 0.001). The risk score was associated with HLA expression, immune checkpoint genes, immune cell infiltration, immune function, tumor mutation burden, tumor stemness score, and drug sensitivity. Lastly, the expression of 11 signature genes was confirmed in glioma tissues.

The disulfidptosis-related gene-based risk score model effectively predicted glioma outcomes and highlighted the role of disulfidptosis-related genes in tumor immunity. This study offers potential new avenues for glioma treatment by targeting disulfidptosis.

Long non-coding RNAs (LncRNAs) are crucial regulators of gene expression and cellular processes, with significant implications for cancer research. This review focuses on the role of LncRNA CARMN (Cardiac Arrest and Regulated Myocyte Nuclear Protein) in various cancers. CARMN, originally identified for its function in cardiac tissues, has shown dysregulated expression in several tumor types, including cervical, breast, colorectal, and esophageal cancers. Its altered expression often correlates with tumor progression, metastasis, and patient prognosis, suggesting its potential as both a biomarker and therapeutic target. In cervical cancer, CARMN's role as a tumor suppressor is highlighted by its ability to inhibit cell proliferation, migration, and invasion through interaction with the miR-92a-3p/BTG2 axis and modulation of the Wnt/β-catenin signaling pathway. In breast cancer, CARMN acts as an enhancer RNA, affecting epithelial-mesenchymal transition and metastasis by regulating MMP2 via DHX9. The downregulation of CARMN in triple-negative breast cancer is associated with enhanced sensitivity to chemotherapy. In colorectal cancer, CARMN's expression is regulated by m6A methylation and mutant p53, influencing tumor growth through miR-5683 and FGF2. Lastly, in esophageal cancer, genetic variations in CARMN affect cancer susceptibility, with certain SNPs and haplotypes associated with either increased or decreased risk. Additionally, the relationship between CARMN and immune cell dynamics highlights its potential role in cancer immune surveillance and therapy. Finally, we found that CARMN may regulate immune cell exhaustion in the tumor microenvironment by influencing the recruitment and activation of NK cells and T cells, as well as modulating macrophage polarization. This review emphasizes the diverse roles of CARMN across different cancers and its potential as a diagnostic and therapeutic tool. Future research should address the mechanistic details of CARMN's involvement in cancer, validate its clinical utility, and explore its therapeutic potential in combination with existing treatments.

Endometrial carcinoma (EC) is one of the most common gynecological malignant tumors, but its underlying pathogenic mechanisms are largely obscure. Interleukin-22 (IL-22), one cytokine in the tumor immune microenvironment, was reported to be associated with carcinoma progression. Here, we aimed to investigate the regulation of IL-22 in endometrial carcinoma. Enzyme-linked immunosorbent assay (ELISA) analysis of IL-22 was done in 27 controls and 51 patients with EC. We examined the proliferative potential, cycle progression, and signaling pathways modulated by IL-22 in EC cells. Western blot analysis was performed to investigate the expression of proliferative and cycle-related proteins in EC cells. The effect of IL-22 mediated by interleukin-22 receptor alpha 1 (IL-22RA1) was examined using cell transfection with small interfering RNA (siRNA). In addition, a xenograft tumor model was performed to assess the effect of IL-22 in vivo. We demonstrated significant up-regulation of serum IL-22 concentrations in EC patients (42.59 ± 23.72 pg/mL) compared to the control group (27.47 ± 8.29 pg/mL). High levels of IL-22 concentrations appear to correlate with malignant clinicopathological features of EC. Treatment with IL-22 promoted cell proliferation and G1/S phase progression in Ishikawa and HEC-1B cells. Western blot analysis revealed that c-Myc, cyclin E1, cyclin-dependent kinase (CDK)2, cyclin D1, CDK4, CDK6, p-extracellular signal-regulated kinase1/2 (p-ERK1/2), and p-p38 were highly expressed in EC cells exposed to IL-22. Moreover, in the EC mice model, we found that giving exogenous IL-22 increased tumor volume and weight. Immunohistochemistry showed that intra-tumor Ki-67 expression was up-regulated upon IL-22 treatment. The IL-22-mediated changes in cell proliferation, cycle progression, and protein expression can be effectively inhibited by the ERK1/2 inhibitor U0126 and the p38 inhibitor SB202190. In addition, the role of IL-22 in EC is receptor-dependent. Our findings suggest that IL-22 promotes endometrial carcinoma cell proliferation and G1/S phase progression by activating ERK1/2 and p38 signaling. Therefore, IL-22 may represent a potential therapeutic target for the treatment of endometrial carcinoma.