The role of neutrophils in defending against infections and regulating immune responses is well-known. In cancer, tumor-associated neutrophils also play a significant role in the progression of tumors. However, the specific mechanisms of their interaction with human colorectal tumors have not been fully elucidated. Our study found that tumor-educated neutrophils can activate the STAT3 signaling pathway in colorectal cancer cells by secreting IL-17a. This leads to increased migration and invasion of colorectal cancer cells, promoting tumor growth by triggering epithelial-to-mesenchymal transition (EMT). These findings suggest that IL-17a secreted by tumor-educated neutrophils contributes to the development of colorectal cancer through the IL-17a/STAT3 signaling pathway. This provides new insights for potential treatments for colorectal cancer.

Neutrophils are integral to the frontline defense against pathogenic bacterial and fungal invasions. Beyond their traditional roles, these cells are increasingly recognized for their dualistic contributions to the pathology of autoimmune and inflammatory diseases, as well as their complex involvement in cancer progression. Neutrophils interact with different disease states, highlighting their potential as therapeutic targets. Within tumor microenvironment (TME), tumor-associated neutrophils (TANs) exhibit a functional dichotomy, capable of either fostering or impeding tumor growth and metastasis. This binary functional potential of TANs, under certain conditions, suggests a reversible state that could transition from tumor-promoting to tumor-eradicating phenotypes. Despite the critical implications of such functional plasticity, systematic studies of TAN behavioral shifts in the context of cancer immunotherapy remain scarce. Herein, we review recent advancements in the understanding of TANs within the TME, highlighting their binary regulatory effects on solid tumors. Leveraging the latest insights from experimental and clinical research, this review elucidates the complex roles of TANs in tumor development and explores their molecular interactions as potential therapeutic targets. The elucidation of these mechanisms holds promise for novel cancer treatment strategies, aiming to improve patient outcomes by manipulating the tumor-promoting or -suppressing functions of TANs.

Radiotherapy, employing high-energy rays to precisely target and eradicate tumor cells, plays a pivotal role in the treatment of various malignancies. Despite its therapeutic potential, the effectiveness of radiotherapy is hindered by the tumor's inherent low radiosensitivity and the immunosuppressive microenvironment. Here we present an innovative approach that integrates peroxynitrite (ONOO-)-mediated radiosensitization with the tumor-associated neutrophils (TANs) polarization for the reversal of immunosuppressive tumor microenvironment (TME), greatly amplifying the potency of radiotherapy. Our design employs X-ray-activated lanthanide-doped scintillators (LNS) in tandem with photosensitive NO precursor to achieve in-situ ONOO- generation. Concurrently, the co-loaded TGF-β inhibitor SB525334, released from the LNS-RS nanoplatform in response to the overexpressed GSH in tumor site, promotes the reprogramming of TANs from N2 phenotype toward N1 phenotype, effectively transforming the tumor-promoting microenvironment into a tumor-inhibiting state. This 'one-two punch' therapy efficiently trigger a robust anti-tumor immune response and exert potent therapeutic effects in orthotopic colorectal cancer and melanoma mouse model. Meanwhile, it also significantly prevents liver metastasis and recurrence in metastatic colorectal cancer. The development of X-ray-controlled platforms capable of activating multiple therapeutic modalities may accelerate the clinical application of radiotherapy-based collaborative therapy.

The parasite of the genus Leishmania is the causative agent of diseases that affect humans called leishmaniasis. These diseases affect millions of people worldwide and the currently existing drugs are either very toxic or the parasites acquire resistance. Therefore, new elimination mechanisms need to be elucidated so that new therapeutic strategies can be developed. Much has already been discussed about the role of neutrophils in Leishmania infection, and their participation is still controversial. A recent study showed that receptors present in the neutrophil membrane, the purinergic receptors, can control the infection when activated, but the triggering mechanism has not been elucidated. In this review, we will address the possible participation of purinergic receptors expressed in the neutrophil extracellular membrane that may be participating in the detection of Leishmania infection and their possible effects during parasitism.

Cachexia is a prevalent multifactorial syndrome characterized by a substantial decrease in food intake, which results from processes such as proteolysis, lipolysis, inflammatory activation, and autophagy, ultimately leading to weight loss. In cancer patients, this condition is referred to as cancer-related cachexia (CRC) and affects over 50% of this population. A comprehensive understanding of the intricate interactions between tumors and the host organism is essential for the development of effective treatments for tumor cachexia. This review aims to elucidate the role of the tumor microenvironment (TME) in the pathogenesis of tumor-associated cachexia and to summarize the current evidence supporting treatment modalities that target the TME.

Malignant tumors of minor salivary glands (MGSTs) are rare and exhibit significant heterogeneity in terms of etiology, histology and prognosis.

This retrospective analysis of 48 resected MGSTs employed Receiver Operating Characteristic (ROC) curves and logistic regression models to evaluate the association between the systemic inflammatory response index (SIRI), the systemic immuno-inflammation index (SII), the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR) with overall survival (OS). Although these biomarkers showed some correlation with OS, none were statistically significant when considered individually.

Significant correlation was observed between the SIRI, SII, and NLR with overall survival (OS). Among these, SIRI was the most reliable predictor, with an area under the curve (AUC) of 0.713, 80% sensitivity, and 70% specificity.

While these inflammatory biomarkers correlate with the prognosis and risk stratification of MGSTs, there is currently no clinical utility in decision making due to the lack of standardization and their limited application in clinical practice.

Despite advances in treatment, liver metastasis remains the predominant pattern of distant spread for colorectal cancer (CRC) and a major cause of cancer-related mortality. DNA Primase Subunit 1 (PRIM1) has been reported to play important roles in cancer progression. This study investigated the role of PRIM1 in CRC liver metastasis, focusing on its influence on neutrophil recruitment and the formation of neutrophil extracellular traps (NETs). In this study, PRIM1 was upregulated in liver metastasis tumor tissues. CCK-8 and Transwell assays showed that the proliferation, migration and invasion of CRC cells were promoted with the ablation of PRIM1 and inhibited with PRIM1 overexpression. For in vivo investigation, we observed that PRIM1 ablation reduced the number and size of metastasis nodules of MC38 cells. Importantly, PRIM1 depletion obviously reduced the percentage of Ly6G+ neutrophils in liver. In contrast, overexpression of PRIM1 reversed these effects. Besides, depletion of neutrophils by anti-Ly6G antibody in mice notably attenuated liver metastasis burden induced by the upregulation of PRIM1. Western blot and immunohistochemistry assays revealed that three chemokines CXCL8, C-GSF and CXCL2 were confirmed to be upregulated with PRIM1 overexpression. Furthermore, PRIM1 overexpression reduced the formation of NETs. These results suggested that PRIM1 could facilitate the liver metastasis of CRC via recruiting neutrophils and NET formation. In conclusion, our novel findings highlighted the important role of PRIM1 in neutrophil recruitment and CRC metastasis and provided new perspectives and potential targets for future research and treatment for CRC.

Our objective was to evaluate the prognostic value of immune infiltration within the intratumoral and peritumoral tissues and to establish a novel histopathology-related immunoscore associated with postoperative colorectal cancer prognosis.

In the tissue microarrays, a total of 104 patients with colorectal cancer were enrolled and randomly assigned to the derivation cohort (n = 61) or the validation cohort (n = 43). Eighteen prognostic immune biomarkers in both intratumoral and peritumoral tissues were examined by the multiplexed immunohistochemistry method, with quantification performed through digital pathology. The histopathology-related immunoscore score was constructed using least absolute shrinkage and selection operator Cox analysis by selected immune features. On the basis of the Cox regression analysis, 3 predictive models were established. Harrell C-statistics were used to assess the performance of those models.

The area under the curve was 0.743 (confidence interval, 0.457-1.000) in the derivation cohort and 0.739 (confidence interval, 0.538-0.940) in the validation cohort. Subsequently, the groups were classified on the basis of the optimal cutoff value, with the high-risk group exhibiting a poorer prognosis. Furthermore, 3 predictive clinical models were constructed, incorporating the significant risk factors and histopathology-related immunoscore score. The first model incorporating both histopathology-related immunoscore score and statistically significant factors identified through univariate analysis demonstrated superior predictive capability for survival across all 3 models, with an area under the curve of 0.852 and C-index of 0.837.

The histopathology-related immunoscore score offers a novel means of estimating of survival in patients with colorectal cancer. These findings indicated that the immunoscore and the clinical factors might serve as complementary tools to TNM staging to improve the accuracy of patient survival prediction.

Oral cavity carcinomas (OCCs) represent roughly 50% of all head and neck cancers. The risk of occult neck metastases for early-stage OCCs ranges from 15 to 35%, thus the need to develop tools that can support the diagnosis detecting these neck metastases. Inflammatory biomarkers and perineural and lympho-vascular invasion are emerging as effective in this field. The aim of this study is to demonstrate the effectiveness of these parameters to detect occult neck metastases in early-stage (T1-T2/N0) OCCs.

A retrospective analysis was conducted on 81 patients surgically treated for early-stage OCC. For all patients, data regarding TNM, pN status after the histopathological examination, inflammatory biomarkers, and perineural and lympho-vascular invasion have been obtained. A statistical analysis was performed using the receiver operating characteristic (ROC) curve to calculate the optimal cutoff values for SII, SIRI, PLR, and NLR.

Fifty-eight patients confirmed N0 status after surgery, while twenty-three resulted pN+. The best cut-off to detect occult neck metastases were PLR 249.30, NLR 13.10, MLR 0.439, SII 1043.12, and SIRI 1.85. The accuracy to detect occult neck metastases was PLR 75%, NLR 81%, MLR 74%, SII 73%, SIRI 70%, perineural invasion 70%, and lympho-vascular invasion 83%.

Our results confirm that inflammatory biomarkers and perineural and lympho-vascular invasion are effective in detecting occult neck metastases in early-stage OCCs. The clinical relevance of this study is that these parameters could be used routinely as preoperative tools to support diagnosis and to help surgeons in the decision-making process, particularly regarding surgical indications for neck lymph nodes treatment.

Colorectal cancer (CRC) stands as one of the tumors with globally high incidence and mortality rates. In recent years, researchers have extensively explored the role of the tumor immune microenvironment (TME) in CRC, highlighting the crucial influence of immune cell populations in driving tumor progression and shaping therapeutic outcomes. The TME encompasses an array of cellular and noncellular constituents, spanning tumor cells, immune cells, myeloid cells, and tumor-associated fibroblasts, among others. However, the cellular composition within the TME is highly dynamic, evolving throughout different stages of tumor progression. These shifts in cell subpopulation proportions lead to a gradual transition in the immune response, shifting from an early antitumor growth to a late-stage environment that supports tumor survival. Therefore, it is crucial to further investigate and understand the complex interactions among the various cell populations within the TME. In this review, we explore the key cellular components of varying origins, subpopulations with shared origins, and noncellular elements within the CRC TME, examining their interconnections and critical considerations for developing personalized and precise immunotherapy strategies.

Cancer is the second leading cause of death among humans worldwide. Despite remarkable improvements in cancer therapies, drug resistance remains a significant challenge. The tumor microenvironment (TME) is intimately associated with therapeutic resistance. Tumor‑associated neutrophils (TANs) are a crucial component of the TME, which, along with other immune cells, play a role in tumorigenesis, development and metastasis. In the current review, the roles of TANs in the TME, as well as the mechanisms of neutrophil‑mediated resistance to cancer therapy, including immunotherapy, chemotherapy, radiotherapy and targeted therapy, were summarized. Furthermore, strategies for neutrophil therapy were discussed and TANs were explored as potential targets for cancer treatment. In conclusion, the need to explore the precise roles, recruitment pathways and mechanisms of action of TANs was highlighted for the purpose of developing therapies that precisely target TANs and reverse drug resistance.

Colorectal cancer (CRC) is the world's third most frequent cancer, and both its incidence and fatality rates are rising. Despite various therapeutic approaches, neither its mortality rate nor its recurrence frequency has decreased significantly. Additionally, conventional treatment approaches, such as chemotherapy and radiotherapy, have several side effects and risks for patients with CRC. Accordingly, the need for alternative and effective treatments for CRC patients is critical. Immunotherapy that utilizes dendritic cells (DCs) harnesses the patient's immune system to combat cancer cells effectively. DCs are the most potent antigen-presenting cells (APCs), which play a vital role in generating anti-cancer T cell responses. A significant barrier to the immune system's ability to eliminate CRC is the establishment of a potent immunosuppressive tumor milieu by malignant cells. Since DCs are frequently defective in this milieu, the tumor setting significantly reduces the effectiveness of DC-based therapy. Determining central mechanisms contributing to tumor growth by unraveling and comprehending the interaction between CRC tumor milieu and DCs may lead to new therapeutic approaches. This study aims to review DC biology and discuss its role in T-cell-mediated anti-tumor immunity, as well as to highlight the immunosuppressive effects of the CRC tumor milieu on the function of DCs. We will also highlight the tumor microenvironment (TME)-related factors that interfere with DC function as a possible therapeutic target to enhance DC-based cell therapy efficacy.

Background: Exosomal programmed death ligand 1 (PD-L1), an exosomal membrane protein found in many tumor types, is consider to aid in regulation of the immune microenvironment. However, the functions and the mechanisms underlying the exosome-mediated regulation of the immune microenvironment in colorectal cancer (CRC) remain unknown. Methods: Western blotting was used to investigate the levels of exosomal PD-L1 in the peripheral blood of patients with CRC and healthy controls. A CRC mouse model was constructed by administering 10 mg/kg azoxymethane (AOM) and dextrane sodium sulfate (DSS) intraperitoneally. The mice were then administered the control or CRC-derived exosomes to examine the regulatory effect of the exosomes on macrophage infiltration and CRC development. In vitro studies, using a coculture system, and flow cytometry analysis were conducted to examine the relationship between the regulatory effect of CRC-derived exosomes on CD4+ T cells and tumor-associated macrophages. RNA-seq and reverse transcription-quantitative polymerase chain reaction assays were used to investigate the mechanisms underlying the regulatory effect of the CRC-derived exosomes on macrophage proliferation and the regulation of the immune microenvironment during CRC development. Results: In patients with CRC, higher levels of exosomal PD-L1 were associated with a more severe form of disease. The treatment of mice with AOM/DSS-induced CRC with CRC-derived exosomes resulted in high levels of macrophage proliferation, increased PD-L1 levels in macrophages, and accelerated CRC progression. Importantly, analysis of an in vitro coculture system and flow cytometry analysis showed that the CRC-derived exosomes transported PD-L1 into macrophages and impaired CD4+ T cell function. Preliminary data suggest that the NF-κb signaling pathway regulates the function of CRC-derived exosomal PD-L1-dependent macrophages. Conclusion: CRC-derived exosomes induce the proliferation of macrophages and increase their PD-L1 levels. They also impair CD4+ T cell function and promote CRC progression. Our findings reveal a novel exosomal PD-L1-mediated crosstalk between the CRC cells and immune cells in the CRC microenvironment.

Neutrophil extracellular trap (NET) has been implicated in cancer progression and metastasis. Nevertheless, the role of the NET-related gene, formyl peptide receptor 1 (FPR1), in osteosarcoma (OS) remains largely unexplored. This study aimed to investigate the prognostic significance and biological function of FPR1 in OS.

The least absolute shrinkage and selection operator (LASSO) algorithm was employed to construct a NET-related prognostic model utilizing OS datasets from TARGET and GEO (GSE21257) databases. The scRNA-seq dataset GSE162454 was then used for verifying the role of NET-related model in OS at single-cell resolution. Next, survival analysis and multivariate cox regression analysis were performed to evaluate the prognostic value of FPR1 in OS patients. The CIBERSORT algorithm was conducted to evaluate the relationship between FPR1 levels and immune cell abundance. Subsequently, the biological role of FPR1 was explored through CCK-8, and transwell assays in OS cell lines.

A signature NET score, comprising four NET-related genes (TNFRSF10C, FPR1, BST1 and SELPLG), was constructed to predict the prognosis of OS. The survival outcomes for patients in high-NET score group were markedly worse than that in the low-NET score group. Meanwhile, at single cell resolution, OS cells progressively evolved into tumors with elevated NET scores. Furthermore, FPR1 levels were markedly reduced in OS cells when compared to normal osteoblast cells, and the overexpression of FPR1 notably suppressed OS cell viability, migration and invasion. Additionally, OS patients exhibiting high levels of FPR1 demonstrated a favorable overall survival. Moreover, these patients also had a higher proportion of M1 macrophages and a lower proportion of M0 macrophages.

Collectively, our study indicates that the NET-related gene FPR1 is closely related to tumor progression, prognosis and immune infiltration in OS.

Background: Oral tongue squamous cell carcinoma (OTSCC) is a common disease that can cause occult metastasis (OM). Methods: This study aims to investigate the role of the pre-treatment neutrophil-to-lymphocyte ratio (NLR) in predicting the presence of neck OM in early-stage OTSCC. We reprocessed the pre-treatment blood data to calculate the NLR and the PLR on patients treated for OTSCC. We used a logistic regression model and the ROC curve to estimate the probability of metastases in cervical lymph nodes using data from pre-surgery blood tests. Results: During the period under review, 113 patients were treated for OTSCC; however, only 74 met the inclusion criteria and were, therefore, enrolled in the study. Twenty-five patients (35.3%) had lymph node metastases, and 46 (64.7%) did not. Without the NLR influence, the probability of metastasis is less than 50% (β0 = -1.058). A higher NLR value means a higher chance of metastasis. This is shown by the positive value of the NLR level coefficient (β1 = 0.135) and the ROC curve (AUC = 0.83). Conclusions: Our study showed a statistical correlation between high pre-treatment NLR values and neck OM in patients with OTSCC. These results may help to identify which patients are at risk of developing OM and then choose the right treatment.

Background/Objectives: Research on colorectal adenoma is significantly less comprehensive compared to studies on colorectal carcinoma. Although colorectal adenoma is a precursor of the majority of sporadic colorectal cancers, not all adenomas develop into carcinomas. The complex interaction of immune responses in the premalignant tumor microenvironment might be a factor for that. Methods: In this systematic review, we aim to provide a thorough analysis of the current research examining the immune infiltration patterns in sporadic colorectal adenoma tissues in the context of immune cell-based, cytokine-based, and other immunological factor-related changes along the conventional adenoma-carcinoma sequence. The articles included in the review extend up to December 2024 in PubMed and Web of Science databases. Results: Most included studies have shown significant differences in immune cell counts, densities, and cytokine expression levels associated with premalignant colorectal lesions (and/or colorectal cancer). No consensus on the immune-related tendencies concerning CD4+T cells and CD8+T cells was reached. Decreasing expression of mDCs and plasma and naïve B cells were detected along the ACS. The increased density of tissue eosinophils in the adenoma tissue dramatically diminishes after the transition to carcinoma. As the adenoma progresses, the increasing expression of IL-1α, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-21, IL-23, IL-33, and TGF-β and decreasing levels of IL-12A, IL-18, IFN-γ, and TNFα cytokines in the invasive carcinoma stage is being detected. The over-expression of COX-2, PD-1/PD-L1, CTLA-4, and ICOS/ICOSLG in the colorectal adenomatous and cancerous tissues was also observed. Conclusions: Further studies are needed for a better understanding of the whole picture of colorectal adenoma-associated immunity and its impact on precancerous lesion's potential to progress.

Background/Objectives: Malignant carcinomas of the salivary glands account for approximately 1 to 7% of all head and neck malignancies and approximately 0.3% of all malignant neoplasms. Recently, the scientific community has focused on finding biomarkers that could tailor the treatment for patients with this type of cancer. The neutrophil-lymphocyte ratio (NLR) was the first marker studied and it is one of the most widely used; the platelet-lymphocyte ratio (PLR), the systemic immune inflammation index (SII) and the systemic inflammatory response index (SIRI) have recently emerged as important biomarkers. The aim of this scoping review is to evaluate the role of inflammatory biomarkers in the management of salivary gland malignancies. Methods: A review of the English literature on inflammatory blood markers in major salivary gland cancer was performed using PubMed, Scopus, and Google Scholar databases. The literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines for scoping reviews. Results: Eleven full-text articles were included in this review, for a total of 1356 patients in which the role of inflammatory biomarkers (NLR, PLR, SII or SIRI) for the diagnosis and prognosis of salivary gland cancer was assessed. NLR (i) was evaluated in all the studies; (ii) it contributed to the diagnosis and prognosis of both adult and pediatric patients and (iii) can be considered the main biomarker, even if a universal cut-off range is not available yet. PLR, SII and SIRI were introduced more recently and were evaluated only in some studies. Conclusions: The findings of this study suggest that elevated NLR values, regardless of age, are more frequently associated with malignancy and a poor prognosis. Further studies are necessary to evaluate the role of biomarkers other than NLR, and to identify universal and practical cut-off values.

Ubiquitin-specific protease 32 (USP32) plays a key role in cancer progression. However, its functions in colorectal carcinoma (CRC) are still unexplored. In our study, we explored the expression and clinical significance of USP32 in CRC as well as its relationship with the tumour microenvironment (TME). As a result, we found that USP32 is overexpressed in CRC and it is associated with poor outcomes in CRC patients. In addition, the expression of USP32 is significantly related to the activation of the NF-κB signalling pathway and the immune infiltrates of the TME. Wet experiments also confirmed that USP32 is critical for the proliferation, survival, and migration of CRC cells and tumour growth, which may be due to the activation of the NF-κB signalling pathway. In conclusion, targeting the USP32-NF-κB axis may be a novel treatment strategy for CRC patients.

Immunotherapy is playing an increasing role in the treatment of various cancers. However, its application in rectal cancer is very limited as only microsatellite-unstable bowel cancers with defective mismatch repair are found to benefit. The majority of rectal cancers belong to the microsatellite-stable phenotype. Therefore, the aim of this study is to explore immune-related genes within the tumor microenvironment of rectal cancer, with the objective of discovering novel biomarkers and therapeutic targets for rectal cancer, and to establish a new prognostic prediction model for rectal cancer based on these immune-related genes.

The data in The Cancer Genome Atlas (TCGA) database were processed using the Estimation of Stromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm to obtain differently expressed genes (DEGs). Then the DEGs were analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Gene and Genomes (KEGG), Reactome function enrichment analysis, and protein-protein interaction (PPI) analysis to screen the core genes, which were utilized to compute the risk scores of individual patients. Finally, combining risk scores and clinical characteristics, a new prognostic prediction model was established by univariate and multivariate Cox analyses, and the prognostic model was validated by the Gene Expression Omnibus (GEO) database.

The study finally identified four core genes (CYBB, CCR4, FOXP3, and CD80), and immune cell infiltration analyses of the four core genes showed that their expression levels were positively correlated with the distribution of various immune cells. The 4-gene risk score categorized rectal cancer patients into high-risk and low-risk groups, and the results showed that the low-risk group had a stronger correlation with the immune response and had a better prognosis. A prognostic model was developed by integrating risk scores and clinical characteristics and showed a strong predictive effect.

In patients with rectal cancer, CYBB, CCR4, FOXP3, and CD80 are immune-related core genes, and low expression of each gene is associated with poor clinical prognosis. The risk score obtained on their basis is independent prognostic factors for rectal cancer, suggesting that the four core genes may provide a foundation for the development of new prognostic biomarkers for rectal cancer and the study of immunotherapy.

Neutrophils, the most abundant myeloid cells in human peripheral blood, serve as the first defense line against infection and are also significantly involved in the initiation and progression of cancer. In colorectal cancer (CRC), neutrophils exhibit a dual function by promoting tumor events and exerting antitumor activity, which is related to the heterogeneity of neutrophils. The neutrophil extracellular traps (NETs), gut microbiota, and various cells within the tumor microenvironment (TME) are involved in shaping the heterogeneous function of neutrophils. This article provides an updated overview of the complex functions and underlying mechanisms of neutrophils in CRC and their pivotal role in guiding prognosis assessment and therapeutic strategies, aiming to offer novel insights into neutrophil-associated treatment approaches for CRC.

Inflammatory Bowel Disease (IBD) is an inflammatory intestinal disease, and with prolonged illness duration, the annual risk of IBD progressing to colitis-associated colorectal cancer (CAC) gradually increases. In recent years, there has been a noticeable trend towards the application of traditional Chinese medicine (TCM) in the treatment of CAC.

This comprehensive review summarizes the pathogenesis of CAC and details the therapeutic benefits of TCM in treating CAC, including various TCM prescriptions and ingredients, establishing the theoretical foundation for the application of TCM in CAC treatment.

We assessed literature published before March 24, 2024, from several databases, including Web of Science, PubMed, Scopus and Google Scholar. The keywords used include "traditional Chinese medicine", "traditional Chinese medicine prescriptions", "traditional Chinese medicine ingredients", "herbal medicine", "colitis-associated colorectal cancer", "inflammatory bowel disease", "colorectal cancer" and "colitis-cancer transformation". We conducted a comprehensive collection and collation of pertinent scientific articles from various databases, focusing on the efficacy of TCM in the prevention and treatment of "colitis-cancer transformation".

This paper provides a concise summary and thorough analysis of twenty-eight prescriptions and ingredients of TCM for the prevention and treatment of CAC, based on existing experimental and clinical research. There are positive signs that TCM can effectively prevent and treat the "colitis-cancer transformation" through repairing the intestinal mucosal barrier, correcting intestinal flora imbalance, and regulating intestinal immune responses.

TCM possesses comprehensive regulatory advantages that are multifaceted, multilevel, and multitarget. It has a definite curative effect in the prevention and treatment of CAC. It is essential to enhance the clinical efficacy of TCM in the prevention and treatment of CAC based on syndrome differentiation and treatment, with the assistance of modern medicine.

Neutrophils, the most abundant circulating leukocytes, have long been recognized as key players in innate immunity and inflammation. However, recent discoveries unveil their remarkable heterogeneity and plasticity, challenging the traditional view of neutrophils as a homogeneous population with a limited functional repertoire. Advances in single-cell technologies and functional assays have revealed distinct neutrophil subsets with diverse phenotypes and functions and their ability to adapt to microenvironmental cues. This review provides a comprehensive overview of the multidimensional landscape of neutrophil heterogeneity, discussing the various axes along which diversity manifests, including maturation state, density, surface marker expression, and functional polarization. We highlight the molecular mechanisms underpinning neutrophil plasticity, focusing on the complex interplay of signaling pathways, transcriptional regulators, and epigenetic modifications that shape neutrophil responses. Furthermore, we explore the implications of neutrophil heterogeneity and plasticity in physiological processes and pathological conditions, including host defense, inflammation, tissue repair, and cancer. By integrating insights from cutting-edge research, this review aims to provide a framework for understanding the multifaceted roles of neutrophils and their potential as therapeutic targets in a wide range of diseases.

Despite the recent advancements in the treatment of cancer, the 5-year survival of patients with non-small cell lung cancer (NSCLC) remains unsatisfactory. Lung adenocarcinoma (LUAD) is NSCLC's most common subtype, and metastasis is the major cause of death in patients with cancer. Therefore, identifying novel targets associated with metastasis in NSCLC is crucial to improving treatment. This study aimed to characterize the expression of GNGT1 in LUAD and to clarify the mechanism underlying the association between the higher expression level of GNGT1 and worse prognosis in patients.

The transcriptome datasets and clinical information of patients with LUAD were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Bioinformatics analyses were performed in 515 patients who were stratified into two groups (high- and low-GNGT1 expression group) according to the GNGT1 level. Overall survival, DNA promotor methylation, immune cell infiltration, gene set enrichment analysis (GSEA), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the functions of GNGT1 and to identify the related hub genes in LUAD. Their expression and functions in LUAD were verified using tissues from patients and transgenic mice overexpressing GNGT1 under the control of a lung-specific promoter (Scgb1a1-Cre).

GNGT1 was overexpressed in patients with LUAD and was associated with poor prognosis. GNGT1 expression was significantly correlated with gene alteration and hypomethylated promoter status. High GNGT1 expression in patients with LUAD was associated with advanced lymph node metastasis and the degree of immune cell infiltration. Functional enrichment analyses indicated that differentially expressed genes (DEGs) in the high-GNGT1 group participated in DNA replication, DNA replication preinitiation, and M phase, while cell adhesion molecules, apoptosis, and natural killer cell-mediated cytotoxicity were all downregulated. Messenger RNA and protein levels were correspondingly regulated in human LUAD tissues and the Scgb1a1-Cre; LSL-GNGT1 mouse model (GNGT1fl/+ mice).

GNGT1 was associated with tumor cell proliferation via the enhancement of tumor cell stemness and interaction with driver genes. Elevated GNGT1 expression promoted epithelial-mesenchymal transformation, remodeled the tumor microenvironment, and led to tumor metastasis, ultimately worsening the survival-related prognosis of patients with LUAD.

Colorectal cancer encompasses a heterogeneous group of malignancies that differ in pathophysiological mechanisms, immune response and infiltration, therapeutic response, and clinical prognosis. Numerous studies have highlighted the clinical relevance of tumor-infiltrating immune cells among different types of colorectal tumors yet vary in cell type definitions and cell identification strategies. The distinction of immune signatures is particularly challenging when several immune subtypes are involved but crucial to identify novel intercellular mechanisms within the tumor microenvironment. In this review, we compile human and non-human studies on tumor-infiltrating immune cells and provide an overview of immune subtypes, their pathophysiological functions, and their prognostic role in colorectal cancer. We discuss how differentiating immune signatures can guide the development of immunotherapeutic targets and personalized treatment regimens. We analyzed comprehensive human protein biomarker profiles across the entire immune spectrum to improve interpretability and application of tumor studies and to ultimately enhance immunotherapy and advance precision medicine for colorectal cancer patients.

Reactive oxygen species (ROS) production and inflammasome activation are the key components of the innate immune response to microbial infection and sterile insults. ROS are at the intersection of inflammation and immunity during cancer development. Balanced regulation of ROS production and inflammasome activation serves as the central hub of innate immunity, determining whether a cell will survive or undergo cell death. However, the mechanisms underlying this balanced regulation remain unclear. Mitochondria and NADPH oxidases are the two major sources of ROS production. Recently, NCF4, a component of the NADPH oxidase complex that primarily contributes to ROS generation in phagocytes, was reported to balance ROS production and inflammasome activation in macrophages. The phosphorylation and puncta distribution of NCF4 shifts from the membrane-bound NADPH complex to the perinuclear region, promoting ASC speck formation and inflammasome activation, which triggers downstream IL-18-IFN-γ signaling to prevent the progression of colorectal cancer (CRC). Here, we review ROS signaling and inflammasome activation studies in colitis-associated CRC and propose that NCF4 acts as a ROS sensor that balances ROS production and inflammasome activation. In addition, NCF4 is a susceptibility gene for Crohn's disease (CD) and CRC. We discuss the evidence demonstrating NCF4's crucial role in facilitating cell-cell contact between immune cells and intestinal cells, and mediating the paracrine effects of inflammatory cytokines and ROS. This coordination of the signaling network helps create a robust immune microenvironment that effectively prevents epithelial cell mutagenesis and tumorigenesis during the early stage of colitis-associated CRC.

N6‑methyladenosine (m6A) is the predominant chemical modification of eukaryotic mRNA, dynamically mediated by the RNA methyltransferase, methyltransferase-like 3 (METTL3). m6A modification plays a critical role in cancer progression through post‑transcriptional regulation in various types of cancer. However, the role of METTL3 and its associated m6A modification in colorectal tumorigenesis remains to be fully elucidated. In the present study, it was demonstrated that METTL3 expression and the m6A levels were both upregulated in colorectal cancer (CRC) and positively associated with clinical progression, based on the bioinformatics analysis of cancer databases. Furthermore, knockdown and overexpression of METTL3 notably affected CRC cell viability, apoptosis and migration in vitro. Similarly, xenograft animal models confirmed that METTL3 promoted CRC tumorigenicity in vivo. Mechanistically, it was revealed that the m6A modification of matrix metallopeptidase 9 (MMP9) mRNA mediated by METTL3 promoted its expression in CRC by decreasing its degradation. Collectively, the findings of the present study suggested that the METTL3/MMP9 axis could serve as a novel promising therapeutic candidate for CRC.

Colorectal cancer (CRC) is often associated with metastasis and recurrence and is the leading cause of cancer-related mortality. In the progression of CRC, recent studies have highlighted the critical role of neutrophils, particularly tumor-associated neutrophils (TANs). TANs have both tumor-promoting and tumor-suppressing activities, contributing to metastasis, immunosuppression, angiogenesis, and epithelial-to-mesenchymal transition. Tumor-promoting TANs promote tumor growth by releasing proteases, reactive oxygen species, and cytokines, whereas tumor-suppressing TANs enhance immune responses by activating T cells and natural killer cells. Understanding the mechanisms underlying TAN mobilization, plasticity, and their role in the tumor microenvironment has revealed potential therapeutic targets. This review provides a comprehensive overview of TAN biology in CRC and discusses both the tumor-promoting and tumor-suppressing functions of neutrophils. Novel therapeutic approaches targeting TANs, such as chemokine receptor antagonists, aim to modulate neutrophil reprogramming and offer promising avenues for improving treatment outcomes of CRC.

Tertiary lymphoid structures (TLS) are ectopic clusters of immune cells found in non-lymphoid tissues, particularly within the tumor microenvironment (TME). These structures resemble secondary lymphoid organs and have been identified in various solid tumors, including colorectal cancer (CRC), where they are associated with favorable prognosis. The role of TLS in modulating the immune response within the TME and their impact on cancer prognosis has garnered increasing attention in recent years.

This review aims to summarize the current understanding of TLS in CRC, focusing on their formation, function, and potential as prognostic markers and therapeutic targets. We explore the mechanisms by which TLS influence the immune response within the TME and their correlation with clinical outcomes in CRC patients.

We conducted a comprehensive review of recent studies that investigated the presence and role of TLS in CRC. The review includes data from histopathological analyses, immunohistochemical studies, and clinical trials, examining the association between TLS density, composition, and CRC prognosis. Additionally, we explored emerging therapeutic strategies targeting TLS formation and function within the TME.

The presence of TLS in CRC is generally associated with an improved prognosis, particularly in early-stage disease. TLS formation is driven by chronic inflammation and is characterized by the organization of B and T cell zones, high endothelial venules (HEVs), and follicular dendritic cells (FDCs). The density and maturity of TLS are linked to better patient outcomes, including reduced recurrence rates and increased survival. Furthermore, the interplay between TLS and immune checkpoint inhibitors (ICIs) suggests potential therapeutic implications for enhancing anti-tumor immunity in CRC.

TLS represent a significant prognostic marker in CRC, with their presence correlating with favorable clinical outcomes. Ongoing research is required to fully understand the mechanisms by which TLS modulate the immune response within the TME and to develop effective therapies that harness their potential. The integration of TLS-focused strategies in CRC treatment could lead to improved patient management and outcomes.

Fusobacterium nucleatum (Fn) has been extensively studied for its connection to colorectal cancer (CRC) and its potential role in chemotherapy resistance. Studies indicate that Fn is commonly found in CRC tissues and is associated with unfavorable prognosis and treatment failure. It has been shown that Fn promotes chemoresistance by affecting autophagy, a cellular process that helps cells survive under stressful conditions. Additionally, Fn targets specific signaling pathways that activate particular microRNAs and modulate the response to chemotherapy. Understanding the current molecular mechanisms and investigating the importance of Fn-inducing chemoresistance could provide valuable insights for developing novel therapies. This review surveys the role of Fn in tumor proliferation, metastasis, and chemoresistance in CRC, focusing on its effects on the tumor microenvironment, gene expression, and resistance to conventional chemotherapy drugs. It also discusses the therapeutic implications of targeting Fn in CRC treatment and highlights the need for further research.

PD-1/PD-L1 blockade therapies have displayed extraordinary clinical efficacy for melanoma, renal, bladder and lung cancer; however, only a minority of colorectal cancer (CRC) patients benefit from these treatments. The efficacy of PD-1/PD-L1 blockade in CRC is limited by the complexities of tumor microenvironment. PD-1/PD-L1 blockade immunotherapy is based on T cell-centered view of tumor immunity. However, the onset and maintenance of T cell responses and the development of long-lasting memory T cells depend on innate immune responses. Acknowledging the pivotal role of innate immunity in anti-tumor immune response, this review encapsulates the employment of combinational therapies those involve PD-1/PD-L1 blockade alongside the activation of innate immunity and explores the underlying cellular mechanisms, aiming to harnessing innate immune responses to induce long-lasting tumor control for CRC patients who received PD-1/PD-L1 blockade therapy.

Colon adenocarcinoma (COAD) is a frequently occurring and lethal cancer. Cuproptosis is an emerging type of cell death, and the underlying pathways involved in this process in COAD remain poorly understood. Transcriptomic and clinical data for COAD patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We investigated alterations in DNA and chromatin of cuproptosis-related genes (CRGs) in COAD. In order to identify predictive differentially expressed genes (DEGs) and various molecular subtypes, we used consensus cluster analysis. Through univariate, multivariate, and Lasso Cox regression analyses, four CRGs were identified. A risk prognostic model for cuproptosis characteristics was constructed based on four CRGs. This study also examined the association between the risk score and the tumor microenvironment (TME), the immune landscape, and drug sensitivity. We distinguished two unique molecular subtypes using consensus clustering analysis. We discovered that the clinical characteristics, prognosis, and TME cell infiltration characteristics of patients with multilayer CRG subtypes were all connected. The internal and external evaluations of the predicted accuracy of the prognostic model built using data derived from a cuproptosis risk score were completed at the same time. A nomogram and a clinical pathological analysis make it more useful in the field of medicine. A significant rise in immunosuppressive cells was observed in the high cuproptosis risk score group, with a correlation identified between the cuproptosis risk score and immune cell infiltration. Despite generally poor prognoses, the patients with a high cuproptosis risk but low tumor mutation burden (TMB), cancer stem cell (CSC) index, or microsatellite instability (MSI) may still benefit from immunotherapy. Furthermore, the cuproptosis risk score positively correlated with immune checkpoint gene expression. Analyzing the potential sensitivity to medications could aid in the development of clinical chemotherapy regimens and decision-making. CRGs are the subject of our in-depth study, which exposed an array of regulatory mechanisms impacting TME. In addition, we performed additional data mining into clinical features, prognosis effectiveness, and possible treatment medications. COAD's molecular pathways will be better understood, leading to more precise treatment options.

This study sought to determine the predictive and prognostic value of clinicopathological parameters and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin (Hgb) level in predicting recurrence patterns and locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) in cervical cancer patients receiving definitive chemoradiotherapy (ChRT).

This study included 261 cervical cancer patients treated with ChRT. The primary endpoints were the predictors of local recurrence (LR) and distant metastasis (DM), whereas the secondary endpoints were LRFS and DMFS. The association of survival with potential prognostic factors was analyzed using Cox regression analysis, and the predictors of LR and DM were identified using logistic regression analysis.

The median follow-up time was 10.9 years. Recurrences occurred in 132 patients (50.6%) within a median of 11.2 months after definitive ChRT. NLR and PLR values were significantly higher in patients with LR and DM than in those without, with no significant differences in Hgb levels in patients with or without LR and DM. In the multivariable logistic regression analysis, lymph node metastasis, elevated NLR, and low Hgb level were significantly correlated with LR and DM. In the multivariable analysis, large tumor size, presence of lymph node metastasis, and elevated NLR were the independent predictors for poor LRFS and DMFS, and Hgb level was an additional prognostic factor for DMFS.

Hematological markers, particularly NLR and Hgb, may serve as cost-effective and readily accessible indicators for predicting recurrence and survival in cervical cancer patients, contributing to their practical use in routine assessments.

Kidney inflammation plays a crucial role in the pathogenesis of IgA nephropathy (IgAN), yet the specific phenotypes of immune cells involved in disease progression remain incompletely understood. Utilizing joint profiling through longitudinal single-cell RNA-sequencing (scRNAseq) and single-cell assay for transposase-accessible chromatin sequencing (scATACseq) can provide a comprehensive framework for elucidating the development of cell subset diversity and how chromatin accessibility regulates transcription.

We aimed to characterize the dynamic immune cellular landscape at a high resolution in an early IgAN mouse model with acute kidney injury (AKI).

A murine model was utilized to mimic 3 immunological states -"immune stability (IS), immune activation (IA) and immune remission (IR)" in early human IgAN-associated glomerulopathy during AKI, achieved through lipopolysaccharide (LPS) injection. Urinary albumin to creatinine ratio (UACR) was measured to further validate the exacerbation and resolution of kidney inflammation during this course. Paired scRNAseq and scATACseq analysis was performed on CD45+ immune cells isolated from kidney tissues obtained from CTRL (healthy vehicle), IS, IA and IR (4 or 5 mice each). The analyses revealed 7 major cell types and 24 clusters based on 72304 single-cell transcriptomes, allowing for the identification and characterization of various immune cell types within each cluster. Our data offer an impartial depiction of the immunological characteristics, as the proportions of immune cell types fluctuated throughout different stages of the disease. Specifically, these analyses also revealed novel subpopulations, such as a macrophage subset (Nlrp1b Mac) with distinct epigenetic features and a unique transcription factor motif profile, potentially exerting immunoregulatory effects, as well as an early subset of Tex distinguished by their effector and cytolytic potential (CX3CR1-transTeff). Furthermore, in order to investigate the potential interaction between immune cells and renal resident cells, we conducted single-cell RNA sequencing on kidney cells obtained from a separate cohort of IS and IA mice without isolating immune cells. These findings underscored the diverse roles played by macrophages and CD8+ T cells in maintaining homeostasis of endothelial cells (ECs) under stress.

This study presents a comprehensive analysis of the dynamic changes in immune cell profiles in a model of IgAN, identifying key cell types and their roles and interactions. These findings significantly contribute to the understanding of the pathogenesis of IgAN and may provide potential targets for therapeutic intervention.

N6-methyladenosine (m6A), the most abundant modification in mRNAs, affects the fate of the modified RNAs at the post-transcriptional level and participants in various biological and pathological processes. Increasing evidence shows that m6A modification plays a role in the progression of many malignancies, including colorectal cancer (CRC). As the only catalytic subunit in methyltransferase complex, methyltransferase-like 3 (METTL3) is essential to the performance of m6A modification. It has been found that METTL3 is associated with the prognosis of CRC and significantly influences various aspects of CRC, such as cell proliferation, invasion, migration, metastasis, metabolism, tumor microcirculation, tumor microenvironment, and drug resistance. The relationship between METTL3 and gut-microbiota is also involved into the progression of CRC. Furthermore, METTL3 might be a viable target for CRC treatment to prolong survival. In this review, we comprehensively summarize the function of METTL3 in CRC and the underlying molecular mechanisms. We aim to deepen understanding and offer new ideas for diagnostic biomarkers and therapeutic targets for colorectal cancer.

Colorectal cancer (CRC) continues to be a major health concern in today's world. Despite conflictive findings, evidence supports systemic inflammation's impact on CRC patients' survival rates. Therefore, this study aims to assess the prognostic role of the innate immune system in patients with CRC.

A total of 449 patients were included, with a 5-year follow-up period, and absolute neutrophil counts and their related ratios were measured.

The non-survival group had increased levels of white blood cells, neutrophils (both p<0.001), and monocytes (p=0.038), compared to the survival group, along with other neutrophil-related ratios. We observed increased mortality risk in patients in the highest tertile of white blood cells [HR=1.85 (1.09-3.13), p<0.05], neutrophils [HR=1.78 (95% CI: 1.07-2.96), p<0.05], and monocytes [HR=2.11 (95% CI: 1.22-3.63)], compared to the lowest tertile, after adjusting for all clinicopathological variables. Random forest analysis identified neutrophils as the most crucial variable in predicting survival rates, having an AUC of 0.712, considering all clinicopathological variables. A positive relationship between neutrophil counts and metastasis was observed when neutrophil counts are considered continuous (β=0.92 (0.41), p<0.05) and tumor size (width) when neutrophils were considered as logistic variable (T1 vs T3) [OR=1.42, (95% CI: 1.05-1.98), p<0.05].

This study offers comprehensive insights into the immune factors that impact the prognosis of CRC, emphasizing the need for personalized prognostic tools.

The liver is one of the most common sites for metastasis, which involves the spread from primary tumors to surrounding organs and tissues in the human body. There are a few steps in cancer expansion: invasion, inflammatory processes allowing the hepatic niche to be created, adhesions to ECM, neovascularization, and secretion of enzymes. The spread of tumor cells depends on the microenvironment created by the contribution of many biomolecules, including proteolytic enzymes, cytokines, growth factors, and cell adhesion molecules that enable tumor cells to interact with the microenvironment. Moreover, the microenvironment plays a significant role in tumor growth and expansion. The secreted enzymes help cancer cells facilitate newly formed hepatic niches and promote migration and invasion. Our study discusses pharmacological methods used to prevent liver metastasis by targeting the tumor microenvironment and cancer cell colonization in the liver. We examine randomized studies focusing on median survival duration and median overall survival in patients administered placebo compared with those treated with bevacizumab, ramucirumab, regorafenib, and ziv-aflibercept in addition to current chemotherapy. We also include research on mice and their responses to these medications, which may suppress metastasis progression. Finally, we discuss the significance of non-pharmacological methods, including surgical procedures, radiotherapy, cryotherapy, radiofrequency ablation (RFA), and transarterial embolization (TAE). In conclusion, the given methods can successfully prevent metastases to the liver and prolong the median survival duration and median overall survival in patients suffering from cancer.

Numerous biomarkers that reflect host status have been identified for patients with metastatic colorectal cancer (mCRC). However, there has been a paucity of biomarker studies that comprehensively indicate body composition, nutritional assessment, and systemic inflammation status. The advanced lung cancer inflammation index (ALI), initially introduced as a screening tool for patients with non-small-cell lung cancer in 2013, emerges as a holistic marker encompassing all body composition, nutritional status, and systemic inflammation status. The index is calculated by the simple formula: body mass index × albumin value / neutrophil-to-lymphocyte ratio. Given its accessibility in routine clinical practice, the ALI has exhibited promising clinical utility in prognosticating outcomes for patients with multiple types of cancer. In this review, we focus on the significance of host status and the clinical applicability of the ALI in the treatment and management of patients with malignancies, including mCRC. We also suggest its potential in guiding the formulation of treatment strategies against mCRC and outline future perspectives.

Colorectal cancer (CRC) is one of the most common cancers worldwide, ranking third in terms of incidence and second as a cause of cancer-related death. There is growing scientific evidence that the gut microbiota plays a key role in the initiation and development of CRC. Specific bacterial species and complex microbial communities contribute directly to CRC pathogenesis by promoting the neoplastic transformation of intestinal epithelial cells or indirectly through their interaction with the host immune system. As a result, a protumoural and immunosuppressive environment is created conducive to CRC development. On the other hand, certain bacteria in the gut microbiota contribute to protection against CRC. In this chapter, we analysed the relationship of the gut microbiota to CRC and the associations identified with specific bacteria. Microbiota plays a key role in CRC through various mechanisms, such as increased intestinal permeability, inflammation and immune system dysregulation, biofilm formation, genotoxin production, virulence factors and oxidative stress. Exploring the interaction between gut microbiota and tumourigenesis is essential for developing innovative therapeutic approaches in the fight against CRC.

Innate immune cells in the colorectal cancer microenvironment mainly include macrophages, neutrophils, natural killer cells, dendritic cells and bone marrow-derived suppressor cells. They play a pivotal role in tumor initiation and progression through the secretion of diverse cytokines, chemokines, and other factors that govern these processes. Colorectal cancer is a common malignancy of the gastrointestinal tract, and understanding the role of innate immune cells in the microenvironment of CRC may help to improve therapeutic approaches to CRC and increase the good prognosis. In this review, we comprehensively explore the pivotal role of innate immune cells in the initiation and progression of colorectal cancer (CRC), alongside an extensive evaluation of the current landscape of innate immune cell-based immunotherapies, thereby offering valuable insights for future research strategies and clinical trials.

Chemokine signaling within the tumor microenvironment can promote tumor progression. Although CCR1 and CXCR2 on myeloid cells could be involved in tumor progression, it remains elusive what effect would be observed if both of those are blocked.

We employed two syngeneic colorectal cancer mouse models: a transplanted tumor model and a liver metastasis model. We generated double-knockout mice for CCR1 and CXCR2, and performed bone marrow (BM) transfer experiments in which sub-lethally irradiated wild-type mice were reconstituted with BM from either wild-type, Ccr1-/-, Cxcr2-/- or Ccr1-/-Cxcr2-/- mice.

Myeloid cells that express MMP2, MMP9 and VEGF were accumulated around both types of tumors through CCR1- and CXCR2-mediated pathways. Mice reconstituted with Ccr1-/-Cxcr2-/- BM exhibited the strongest suppression of tumor growth and liver metastasis compared with other three groups. Depletion of CCR1+CXCR2+ myeloid cells led to a higher frequency of CD8+ T cells, whereas the numbers of Ly6G+ neutrophils, FOXP3+ Treg cells and CD31+ endothelial cells were significantly decreased. Furthermore, treatment with a neutralizing anti-CCR1 mAb to mice reconstituted with Cxcr2-/- BM significantly suppressed tumor growth and liver metastasis.

Dual blockade of CCR1 and CXCR2 pathways in myeloid cells could be an effective therapy against colorectal cancer.