Inflammasomes are multi-protein complexes that detect pathogenic and damage-associated molecular patterns, activating caspase-1, pyroptosis, and the maturation of pro-inflammatory cytokines such as IL-1β and IL-18Within the tumor microenvironment, inflammasomes like NLRP3 play critical roles in cancer initiation, promotion, and progression. Their activation influences the crosstalk between innate and adaptive immunity by modulating immune cell recruitment, cytokine secretion, and T-cell differentiation. While inflammasomes can contribute to tumor growth and metastasis through chronic inflammation, their components also present novel therapeutic targets. Several inhibitors targeting inflammasome components- such as sensor proteins (e.g., NLRP3, AIM2), adaptor proteins (e.g., ASC), caspase-1, and downstream cytokines- are being explored to modulate inflammasome activity. These therapeutic strategies aim to modulate inflammasome activity to enhance anti-tumor immune responses and improve clinical outcomes. Understanding the role of inflammasomes in cancer immunity is crucial for developing interventions that effectively bridge innate and adaptive immune responses for better therapeutic outcomes.

Activation of the epithelial-mesenchymal transition (EMT), a pivotal process in tumor metastasis and evasion, as well as the NLRP3 inflammasome, both promote colorectal cancer (CRC) progression. Recent studies have shown that Transmembrane protein 176B (TMEM176B) regulates NLRP3 and promotes CRC malignant phenotypes.

To investigate the role of TMEM176B in modulating NLRP3 inflammasome and its implications on EMT and tumor progression in CRC.

CRC in situ mouse and co-cultured cell models were established using CT26 cells, BALB/c mice, and primary cultured mouse natural killer (NK) cells. Short hairpin RNA knocked down TMEM176B and NLRP3 expression in CT26 cells. Fluorescence imaging, Terminal deoxynucleotidyl transferase dUTP nick end labeling assays, immunohistochemistry staining, flow cytometry, and molecular assays were used to investigate the effects of TMEM176B knockdown on the NLRP3 inflammasome in NK cells to assess tumor metastasis, apoptosis, and EMT indicators.

Silencing TMEM176B in CRC mice significantly reduced tumor metastasis, proliferation, and EMT, while activating apoptosis, NLRP3 inflammasome, and NK cell activity. Furthermore, silencing TMEM176B in co-cultured cell models inhibited cell migration and invasion, and promoted apoptosis. The interference of NLRP3 reversed these effects by modulating key proteins such as phosphorylated nuclear factor kappa B subunit 1 p65, matrix metallopeptidase 9, and transforming growth factor-β.

This study highlights the critical role of TMEM176B/NLRP3 in CRC progression and provides a basis for targeting this axis as a novel therapeutic approach to manage CRC progression and metastasis.

Although photothermal therapy (PTT) can induce antitumour immunity, the mechanisms underlying its effects in pancreatic cancer (PC) require further exploration. In this study, the mechanism of action of PTT and its connection to pyroptosis as well as the therapeutic potential of PTT alone and in combination with STING agonists, were investigated. In addition, a biomarker of PC was found to stratify patients who are suitable for PTT.

We explored whether PTT can induce pyroptosis in vitro and evaluated the therapeutic efficacy and antitumour immunity-inducing ability of PTT combined with STING agonist (c-di-GMP) as immune adjuvant in vivo in PC. We also evaluated gasdermin D (GSDMD) expression in tumour tissues and investigated drug sensitivity in patient-derived organoids (PDOs) with differential GSDMD expression.

Our study demonstrated that local PTT induces pyroptosis via the caspase-1/GSDMD pathway and elicits antitumour immunity. PTT combined with a STING agonist exhibits better therapeutic efficacy than PTT alone while limiting distant tumour metastasis, and enhances the immune response by promoting dendritic cell maturation, increasing the frequency of tumour infiltrating T cells, and converting macrophages from the M2 to the M1 phenotype. In addition, we found that GSDMD is highly expressed in tumour tissues and that overexpression of GSDMD in PC might suggest increased resistance to chemotherapy and the potential benefits of local therapy. We further confirmed that PDOs with higher GSDMD expression are less sensitive to a chemotherapeutic agent (5-Fluorouracil) than PDOs with lower GSDMD expression, making GSDMD a new biomarker for identifying patients who may benefit from PTT.

In this work, c-di-GMP was used as an immune adjuvant for PTT to treat PC for the first time, and the results provide clues for the development of novel combination immunotherapies that simultaneously suppress primary tumours and distant metastases. GSDMD has great potential as a new biomarker for the selection of individualized treatment modalities.

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous obstructive diseases characterized by airflow limitations and are recognized as significant contributors to fatality all over the globe. Asthma accounts for about 4, 55,000 deaths, and COPD is the 3rd leading contributor of mortality worldwide. The pathogenesis of these two obstructive disorders is complex and involves numerous mechanistic pathways, including inflammation-mediated and non-inflammation-mediated pathways. Among all the pathological categorizations, programmed cell deaths (PCDs) play a dominating role in the progression of these obstructive diseases. The two major PCDs that are involved in structural and functional remodeling in the progression of asthma and COPD are Pyroptosis and Ferroptosis. Pyroptosis is a PCD mechanism mediated by the activation of the Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome, leading to the maturation and release of Interleukin-1β and Interleukin-18, whereas ferroptosis is a lipid peroxidation-associated cell death. In this review, the major molecular pathways contributing to these multifaceted cell deaths have been discussed, and crosstalk among them regarding the pathogenesis of asthma and COPD has been highlighted. Further, the possible therapeutic approaches that can be utilized to mitigate both cell deaths at once have also been illustrated.

Breast cancer is a prevalent malignancy worldwide, and its treatment has increasingly shifted towards precision medicine, with immunotherapy emerging as a key therapeutic strategy. Deubiquitination, an essential epigenetic modification, is regulated by deubiquitinating enzymes (DUBs) and plays a critical role in immune function and tumor progression. Ubiquitin-specific proteases (USPs), a prominent subgroup of DUBs, are involved in regulating immune cell functions, antigen processing, and T cell development in the context of breast cancer. Certain USPs also modulate the differentiation of immune cells, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), within the breast cancer immune microenvironment. Furthermore, several USPs influence the expression of PD-L1, thus affecting the efficacy of immune checkpoint inhibitors. The overexpression of USPs may promote immune evasion, contributing to the development of treatment resistance. This review elucidates the role of USPs in modulating the immune microenvironment and immune responses in breast cancer. Additionally, it discusses effective strategies for combining USP inhibitors with other therapeutic agents to enhance treatment outcomes. Therefore, targeting USPs presents the potential to enhance the efficacy of immunotherapy and overcome drug resistance, offering a more effective treatment strategy for breast cancer patients.

The progression of melanoma is a complex process influenced by both internal and external cues which encourage the transition of tumour cells, uncontrolled growth, migration, and metastasis. Additionally, inflammation allows tumours to evade the immune system, contributing to cancer development. The inflammasome, a complex of many proteins, is crucial in enhancing immune responses to external and internal triggers. As a critical inflammatory mechanism, it contributes to the development of melanoma. These mechanisms may be triggered via various internal and external stimuli, causing the induction of specific enzymes such as caspase-1, caspase-11, or caspase-8. This, in turn, leads to the release of interleukin (IL)-1β and IL-18 and cell death by apoptosis and pyroptosis. Proper inflammasome stimulation is crucial for the host to deal with invading pathogens or tissue injury. However, inappropriate inflammasome stimulation can result in unregulated tissue reactions, thus easing many diseases, including melanoma. Hence, keeping a delicate equilibrium between the stimulation and prohibition of inflammasomes is crucial, necessitating meticulous control of the assembly and functional aspects of inflammasomes. This review examines the latest advancements in inflammasome studies, specifically focusing on the molecular processes that control inflammasome formation, signalling, and modulation in melanoma.

The NLRP3 inflammasome plays a pivotal role in host defense and drives inflammation against microbial threats, crystals, and danger-associated molecular patterns (DAMPs). Dysregulation of NLRP3 activity is associated with various human diseases, making it an attractive therapeutic target. Patients with NLRP3 mutations suffer from Cryopyrin-Associated Periodic Syndrome (CAPS) emphasizing the clinical significance of modulating NLRP3. In this study, we present the identification of a novel chemical class exhibiting selective and potent inhibition of the NLRP3 inflammasome. Through a comprehensive structure-activity relationship (SAR) campaign, we optimized the lead molecule, compound A, for in vivo applications. Extensive in vitro and in vivo characterization of compound A confirmed the high selectivity and potency positioning compound A as a promising clinical candidate for diseases associated with aberrant NLRP3 activity. This research contributes to the ongoing efforts in developing targeted therapies for conditions involving NLRP3-mediated inflammation, opening avenues for further preclinical and clinical investigations.

Hepatocellular carcinoma is among the most frequent forms of primary liver cancer and develops within a context of chronic inflammation, frequently associated with a multitude of risk factors, including viral infections, metabolic dysfunction-associated fatty liver disease, metabolic dysfunction-associated steatohepatitis and liver fibrosis. The tumor microenvironment is crucial for the progression of HCC, as immune cells, tumor-associated fibroblasts and hepatic stellate cells interact to promote chronic inflammation and tumor spread. Inflammasomes, the multiprotein complexes that launch the innate immune response, emerge as important mediators in the pathogenesis of HCC. Among others, the inflammasome Nucleotide-binding oligomerization domain, Leucine rich Repeat (NLR) and Pyrin (NLRP) 3 (NLRP3), and absent in melanoma 2 (AIM2), exhibit a dual role in HCC background. It has been reported that they can exert oncosuppressive functions by triggering the inflammatory death of cancer cells. Vice versa, chronic activation contributes to the development of a pro-tumorigenic environment, thus supporting tumor growth. In addition, other inflammasomes such as Nucleotide-binding oligomerization domain, Leucine rich Repeat (NLR) and Pyrin (NLRP) 6 and 12 (NLRP6 and NLRP12, respectively) regulate HCC onset and progression, although more experimental evidence is required. This review focuses on the molecular mechanisms underpinning the inflammasome's contribution to the onset, progression and spread of HCC. Moreover, we will explore the potential therapeutic approaches currently under investigation, which aim to improve the efficacy and reduce the side effects of the treatments currently available. Targeting inflammasomes may be a promising therapeutic strategy for the treatment of HCC, offering new opportunities to improve patient prognosis.

Inflammation can affect the progression of cancer at tumor sites, such as in osteosarcoma, by intensifying metastasis and complicating outcomes. The current diagnostic methods lack the specificity and sensitivity required for early and accurate detection, particularly in differentiating between inflammation-induced changes and tumor activities. To address this, a novel "hedgehog ball"-shaped nanoprobe, Fe3O4@Au-pep-CQDs, was developed and designed to enhance the detection of caspase-1, a key marker of inflammation. This magnetic nanoprobe facilitates simultaneous fluorescence (FL) and electrochemiluminescence (ECL) detection. Magnetic separation minimizes the quenching of nanoparticles in solution and eliminates the need for frequent electrode replacement in ECL tests, thereby simplifying diagnostic procedures. The experimental results showed that in the detection of caspase-1, the nanoprobe had a detection limit of 0.029 U/mL (FL) and 0.033 U/mL (ECL) and had a dynamic range of 0.05 to 1.0 U/mL. Additionally, the nanoprobe achieved high recovery rates of 94.36 to 102.44% (FL) and 94.36-100.12% (ECL) in spiked biological samples. Furthermore, the nanoprobe's capabilities were extended to in vivo bioimaging to provide direct, intuitive visualization of biological processes. These novel nanoprobes were able to significantly enhance the accurate detection of inflammation at tumor sites, thereby optimizing both diagnostic and therapeutic strategies.

Dysregulated activation of the innate immune system is a critical driver of chronic inflammation that is associated with at least 30% of all cancers. Innate immunity can also exert tumour-promoting effects (e.g. proliferation) directly on cancer cells in an intrinsic manner. Conversely, innate immunity can influence adaptive immunity-based anti-tumour immune responses via Ag-presenting dendritic cells that activate natural killer and cytotoxic T cells to eradicate tumours. While adaptive anti-tumour immunity has underpinned immunotherapy approaches with immune checkpoint inhibitors and chimeric Ag receptor-T cells, the clinical utility of innate immunity in cancer is underexplored. Innate immune responses are governed by pattern recognition receptors, which comprise several families, including Toll-like, nucleotide-binding oligomerization domain-containing (NOD)-like and absent-in-melanoma 2 (AIM2)-like receptors. Notably, a subset of NOD-like and AIM2-like receptors can form large multiprotein "inflammasome" complexes which control maturation of biologically active IL-1β and IL-18 cytokines. Over the last decade, it has emerged that inflammasomes can coordinate contrasting pro- and anti-tumour responses in cancer and non-cancer (e.g. immune, stromal) cells. Considering the importance of inflammasomes to the net output of innate immune responses, here we provide an overview and discuss recent advancements on the diverse role of inflammasomes in cancer that have underpinned their potential targeting in diverse malignancies.

Does the NOD-like receptor protein 3 (NLRP3) inflammasome have an effect in adenomyosis?

Fresh-frozen endometrial tissues and paraffin specimens were obtained from endometrial tissues from patients with adenomyosis and controls. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were applied to assess expression of the NLRP3 inflammasome components. Primary eutopic endometrial stromal cells were isolated from the uteri of patients with adenomyosis. After NLRP3 was knocked down using small interfering RNA, proliferation, invasion and epithelial-mesenchymal transition (EMT) were evaluated using EdU, CCK8, transwell assays and western blot. Importantly, a mouse model of adenomyosis was established to evaluate the effects of the NLRP3 inhibitor MCC950 on the formation of adenomyosis.

Expression of the NLRP3 inflammasome components was elevated in the ectopic or eutopic endometrium of patients with adenomyosis. NLRP3 knockdown inhibited migration, invasion and EMT in endometrial cells and primary endometrial cells (P < 0.0001). MCC950, which blocks the NLRP3 inflammasome, reduced migration and invasion of endometrial cells (P < 0.01) and primary endometrial cells (P < 0.0001) considerably. Importantly, in the mouse model of adenomyosis, MCC950 had a mitigating effect on the severity of adenomyosis (P < 0.01).

NLRP3 was found to enhance migration, invasion and EMT of human endometrial cells in adenomyosis. Notably, the NLRP3 inhibitor MCC950 reduced migration and invasion of endometrial cells effectively. Furthermore, in the mouse model of adenomyosis, MCC950 exhibited a therapeutic effect by alleviating the severity of adenomyosis.

Contemporary progress in tumor immunotherapy has solidified its role as an effective approach in combating cancer. Nonetheless, the prevalent "immune cold" state within the tumor microenvironment poses a substantial barrier to its efficacy. Addressing this, pyroptosis-a gasdermin-mediated programmed cell death characterized by its inflammatory profile-emerges as a crucial mechanism. It catalyzes the release of vast quantities of pro-inflammatory cytokines and immunogens, potentially transforming immunosuppressive "cold" tumors into reactive "hot" ones. Herein, we will initially present an overview of pyroptosis as a distinct form of cell death, along with its molecular mechanisms. Subsequently, we will focus on introducing how pyroptosis activators are utilized in the field of tumor immunotherapy. Insights gained from applications of pyroptosis activators in tumor immunotherapy could lead to the development of safe and efficient pyroptosis activators, significantly enriching the arsenal for tumor immunotherapy.

Today, cancer treatment is one of the main challenges for researchers. The main cause of tumor cell formation is mutations that lead to uncontrolled proliferation and inhibition of apoptosis in malignant cells. Tumor cells also create a microenvironment that can suppress the immune system cells' responses through various methods, including producing soluble factors and cell-to-cell communication. After being produced from tumor cells, exosomes can also affect the functions of other cells in this microenvironment. Various studies have shown that exosomes from different sources, including tumor cells and immune cells, can be used to treat cancers due to their characteristics. Since tumor cells are rich sources of various types of tumor peptides, they can induce anti-tumor responses. Immune cells also produce exosomes that mimic the functions of their cells of origin, such that exosomes derived from NK cells and CTLs can directly lead to their apoptosis after merging with tumor cells. However, many researchers have pointed out that naïve exosomes have a limited therapeutic function, and their therapeutic potential can be increased by manipulating and engineering them. There are various methods to modify exosomes and improve their therapeutic potential. In general, these methods are divided into two parts, which include changing the cell of origin of the exosome and encapsulating the exosome to carry different drugs. In this review, we will discuss the studies on the therapeutic use of naive and engineered exosomes and provide an update on new studies in this field.

Pyroptosis is a cell death process characterized by cell swelling until membrane rupture and release of intracellular contents. As an effective tumor treatment strategy, inducing tumor cell pyroptosis has received widespread attention. In this process, the immune components within the tumor microenvironment play a key regulatory role. By regulating and altering the functions of immune cells such as cytotoxic T lymphocytes, natural killer cells, tumor-associated macrophages, and neutrophils, tumor cell pyroptosis can be induced. This article provides a comprehensive review of the molecular mechanisms of cell pyroptosis, the impact of the tumor immune microenvironment on tumor cell pyroptosis, and its mechanisms. It aims to gain an in-depth understanding of the communication between the tumor immune microenvironment and tumor cells, and to provide theoretical support for the development of new tumor immunotherapies.

Neutrophils, major regulator of innate immunity have recently emerged as key components of the tumor microenvironment. The role of neutrophils in cancer has been linked to their ability to form neutrophil extracellular traps (NETs), structures composed of decondensed DNA decorated with enzymes that are released into the extracellular space. Here, we discuss the pivotal roles of NETs, in influencing responses to chemotherapy and its severe adverse effect. Highlighting recent insights, we discuss the dual nature of NETs in the context of chemotherapy treatment, examining their potential to either counteract or enhance treatment outcomes. Strategic targeting of NETs emerges as a promising avenue for determining combination therapies that could help counteracting resistance or enhancing chemotherapy efficacy as well as limiting complications due to this type of treatment.

Glioblastoma (GBM) is the most common malignant brain tumor and has a dismal prognosis even under the current first-line treatment, with a 5-year survival rate less than 7%. Therefore, it is important to understand the mechanism of treatment resistance and develop new anti-tumor strategies. Induction of programmed cell death (PCD) has become a promising anti-tumor strategy, but its effectiveness in treating GBM remains controversial. On the one hand, PCD triggers tumor cell death and then release mediators to draw in immune cells, creating a pro-inflammatory tumor microenvironment (TME). One the other hand, mounting evidence suggests that PCD and inflammatory TME will force tumor cells to evolve under survival stress, leading to tumor recurrence. The purpose of this review is to summarize the role of PCD and inflammatory TME in the tumor evolution of GBM and promising methods to overcome tumor evolution.

Breast cancer is a prevalent and severe form of cancer that affects women all over the world. The incidence and mortality of breast cancer continue to rise due to factors such as population growth and the aging of the population. There is a growing area of research focused on a cell death mechanism known as PANoptosis. This mechanism is primarily regulated by the PANoptosome complex and displays important characteristics of cell death, including pyroptosis, apoptosis, and/or necroptosis, without being strictly defined by the cell death pathway. PANoptosis acts as a defensive response to external stimuli and pathogens, contributing to the maintenance of cellular homeostasis and overall stability. Increasing evidence suggests that programmed cell death (PCD) plays an important role in the development of breast cancer, and PANoptosis, as a novel form of PCD, may be a crucial factor in the development of breast cancer, potentially leading to the identification of new therapeutic strategies. Therefore, the concept of PANoptosis not only deepens our understanding of PCD, but also opens up new avenues for treating malignant diseases, including breast cancer. This review aims to provide an overview of the definition of PANoptosis, systematically explore the interplay between PANoptosis and various forms of PCD, and discuss its implications for breast cancer. Additionally, it delves into the current progress and future directions of PANoptosis research in the context of breast cancer, establishing a theoretical foundation for the development of molecular targets within critical signaling pathways related to PANoptosis, as well as multi-target combination therapy approaches, with the goal of inducing PANoptosis as part of breast cancer treatment.

Gastric cancer (GC) is a prevalent form of malignancy characterized by significant heterogeneity. The development of a specific prediction model is of utmost importance to improve therapy alternatives. The presence of H. pylori can elicit pyroptosis, a notable carcinogenic process. Furthermore, the administration of chemotherapeutic drugs is often employed as a therapeutic approach to addressing this condition. In the present investigation, it was observed that there were variations in the production of 17 pyroptosis-regulating proteins between stomach tissue with tumor development and GC cells. The predictive relevance of each gene associated with pyroptosis was assessed using the cohort from the cancer genome atlas (TCGA). The least absolute shrinkage and selection operator (LASSO) was utilized to enhance the outcomes of the regression approach. Patients with gastric cancer GC in the cohort from the TCGA were categorized into low-risk or high-risk groups based on their gene expression profiles. Patients with a low risk of gastric cancer had a higher likelihood of survival compared to persons classified as high risk (P<0.0001). A subset of patients diagnosed with GC from a Genes Expression Omnibus (GEO) cohort was stratified according to their overall survival (OS) duration. The statistical analysis revealed a higher significance level (P=0.0063) regarding OS time among low-risk individuals. The study revealed that the GC risk score emerged as a significant independent prognostic factor for OS in patients diagnosed with GC. The results of Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) research revealed that genes associated with a high-risk group had significantly elevated levels of immune system-related activity. Furthermore, it was found that the state of immunity was diminished within this particular group. The relationship between the immune response to cancer and pyroptosis genes is highly interconnected, suggesting that these genes have the potential to serve as prognostic indicators for GC.

Macrophages are highly plastic cells ubiquitous in various tissues, where they perform diverse functions. They participate in the response to pathogen invasion and inflammation resolution following the immune response, as well as the maintenance of homeostasis and proper tissue functions. Macrophages are generally considered long-lived cells with relatively strong resistance to numerous cytotoxic factors. On the other hand, their death seems to be one of the principal mechanisms by which macrophages perform their physiological functions or can contribute to the development of certain diseases. In this review, we scrutinize three distinct pro-inflammatory programmed cell death pathways - pyroptosis, necroptosis, and ferroptosis - occurring in macrophages under specific circumstances, and explain how these cells appear to undergo dynamic yet not always final changes before ultimately dying. We achieve that by examining the interconnectivity of these cell death types, which in macrophages seem to create a coordinated and flexible system responding to the microenvironment. Finally, we discuss the complexity and consequences of pyroptotic, necroptotic, and ferroptotic pathway induction in macrophages under two pathological conditions - atherosclerosis and cancer. We summarize damage-associated molecular patterns (DAMPs) along with other microenvironmental factors, macrophage polarization states, associated mechanisms as well as general outcomes, as such a comprehensive look at these correlations may point out the proper methodologies and potential therapeutic approaches.

Inflammasomes are cytoplasmic protein complexes that play a crucial role in protecting the host against pathogenic and sterile stressors by initiating inflammation. Upon activation, these complexes directly regulate the proteolytic processing and activation of proinflammatory cytokines interleukin (IL)-1β and IL-18 to induce a potent inflammatory response, and induce a programmed form of cell death called pyroptosis to expose intracellular pathogens to the surveillance of the immune system, thus perpetuating inflammation. There are various types of inflammasome complexes, with the NLRP1 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-1) inflammasome being the first one identified and currently recognized as the predominant inflammasome sensor protein in human keratinocytes. Human NLRP1 exhibits a unique domain structure, containing both an N-terminal pyrin (PYD) domain and an effector C-terminal caspase recruitment domain (CARD). It can be activated by diverse stimuli, such as viruses, ultraviolet B radiation and ribotoxic stress responses. Specific mutations in NLRP1 or related genes have been associated with rare monogenic skin disorders, such as multiple self-healing palmoplantar carcinoma; familial keratosis lichenoides chronica; autoinflammation with arthritis and dyskeratosis; and dipeptidyl peptidase 9 deficiency. Recent research breakthroughs have also highlighted the involvement of dysfunctions in the NLRP1 pathway in a handful of seemingly unrelated dermatological conditions. These range from monogenic autoinflammatory diseases to polygenic autoimmune diseases such as vitiligo, psoriasis, atopic dermatitis and skin cancer, including squamous cell carcinoma, melanoma and Kaposi sarcoma. Additionally, emerging evidence implicates NLRP1 in systemic lupus erythematosus, pemphigus vulgaris, Addison disease, Papillon-Lefèvre syndrome and leprosy. The aim of this review is to shed light on the implications of pathological dysregulation of the NLRP1 inflammasome in skin diseases and investigate the potential rationale for targeting this pathway as a future therapeutic approach.

Pyroptosis, a new form of inflammatory programmed cell death, has recently gained attention. However, the impact of the expression levels of pyroptosis-related genes (PRGs) on the overall survival (OS) of osteosarcoma patients remains unclear. This study aims to investigate the impact of the expression levels of PRGs on the OS of pediatric and young adult patients with osteosarcoma.

Transcriptome matrix datasets of normal muscle or skeletal tissues from the Genotype-Tissue Expression (GTEx) project and osteosarcoma specimen the National Cancer Institute's (NCI) Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were used to identify pyroptosis-related genes (PRGs) associated with prognosis. The National Center for Biotechnology Information's (NCBI) GSE21257 dataset was employed to validate the predictive value of the pyroptosis-related signature (PRS). Additionally, reverse transcription polymerase chain reaction (RT-qPCR) experiment was performed in normal and osteosarcoma cell lines.

The study identified 18 differentially expressed PRGs (DEPRGs) between normal muscle or skeletal tissues and tumor samples. Multiple machine learning techniques were used to select PRGs, resulting in the identification of four hub PRGs. A PRS-score was calculated for each sample based on the expression of these four hub PRGs, and samples were categorized into low and high PRS-score level groups. It was confirmed that metastatic status and PRS-score level are independent prognostic predictors. A nomogram model for predicting OS of osteosarcoma patients was constructed. Single-cell RNA-sequencing data display the expression patterns of the hub PRGs. RT-qPCR data results were found to be consistent with the differential expression analysis performed on TARGET and GTEx samples.

The study developed a novel pyroptosis-related gene signature that can stratify pediatric and young adult osteosarcoma patients into different risk groups, thus predicting their response to immunotherapy and chemotherapy.

Pancreatic cancer is a malignant neoplasm that, despite its low frequency, has a 5-year survival rate of less than 10%. The study of different histopathological markers has allowed a better understanding of the onset and development of this type of tumor as well as facilitating an approach to clinical variables based on their diagnostic, prognostic, and predictive value. In this sense, the NLRP3 protein of the inflammasome has been shown to be a component of great relevance in the initiation and progression of pancreatic cancer, although the value of this biomarker in patients has not yet been clarified. In this study, we selected 41 patients with pancreatic cancer and followed them for 60 months (5 years), evaluating their NLRP3 expression using immunohistochemical techniques. Furthermore, by performing Kaplan-Meier curves, we evaluated the survival of these patients in relation to their NLRP3 expression. Our results show that a significant percentage of our cohort had high expression of this component (90.74%) and that there is an inverse relationship between the expression of NLRP3 and patient survival. High levels of NLRP3 expression are related to lower survival and worse prognosis in these patients, possibly due to an ineffective immune system response and increased tumor-promoted inflammation. Future studies should be aimed at confirming these results in larger groups and evaluating various clinical strategies based on this knowledge.

Interleukin-33 (IL-33) and its receptor Serum Stimulation-2 (ST2, also called Il1rl1) are members of the IL-1 superfamily that plays a crucial role in allergic diseases. The interaction of IL-33 and ST2 mainly activates NF-κB signaling and MAPK signaling via the MyD88/IRAK/TRAF6 module, resulting in the production and secretion of pro-inflammatory cytokines. The IL-33/ST2 axis participates in the pathogenesis of allergic diseases, and therefore serves as a promising strategy for allergy treatment. In recent years, strategies blocking IL-33/ST2 through targeting regulation of IL-33 and ST2 or targeting the molecules involved in the signal transduction have been extensively studied mostly in animal models. These studies provide various potential therapeutic agents other than antibodies, such as small molecules, nucleic acids and traditional Chinese medicines. Herein, we reviewed potential targets and agents targeting IL-33/ST2 axis in the treatment of allergic diseases, providing directions for further investigations on treatments for IL-33 induced allergic diseases.

Research has shown that pyroptosis contributes greatly to the progression of diabetes and its complications. However, the exact relationship between this particular cell death process and the pathology of type 2 diabetes mellitus (T2DM) remains unclear. In this study, we used bioinformatic tools to identify the pyroptosis-related genes (PRGs) associated with T2DM and to analyze their roles in the disease pathology.

Two microarray datasets, GSE7014 and GSE25724, were obtained from the GEO database and assessed for differentially expressed genes (DEGs). The T2DM-associated DEGs that overlapped with differentially expressed PRGs were noted as T2DM-PRGs. Subsequently, 25 T2DM-PRGs were validated and subjected to functional enrichment analysis through Gene Ontology annotation analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and gene set enrichment analysis (GSEA). The diagnostic and predictive value of the T2DM-PRGs was evaluated using receiver operating characteristic curves (ROC). Additionally, a single-sample GSEA algorithm was applied to study immune infiltration in T2DM and assess immune infiltration levels.

We identified 25 T2DM-PRGs that were significantly enriched in the nuclear factor-kappa B signaling and prostate cancer pathways. The top five differentially expressed prognostic T2DM-PRGs targeted by miRNAs were PTEN, BRD4, HSP90AB1, VIM, and PKN2. The top five differentially expressed T2DM-PRGs associated with transcription factors were HSP90AB1, VIM, PLCG1, SCAF11, and PTEN. The genes PLCG1, PTEN, TP63, CHI3L1, SDHB, DPP8, BCL2, SERPINB1, ACE2, DRD2, DDX58, and BTK showed excellent diagnostic performance. The immune infiltration analysis revealed notable differences in immune cells between T2DM and normal tissues in both datasets. These findings suggest that T2DM-PRGs play a crucial role in the development and progression of T2DM and could be used as potential diagnostic biomarkers and therapeutic targets.

Investigating the mechanisms and biomarkers associated with pyroptosis may offer valuable insights into the pathophysiology of T2DM and lead to novel therapeutic approaches to treat the disease.

Pyroptosis, a novel form of programmed cell death (PCD) discovered after apoptosis and necrosis, is characterized by cell swelling, cytomembrane perforation and lysis, chromatin DNA fragmentation, and the release of intracellular proinflammatory contents, such as Interleukin (IL) 8, IL-1β, ATP, IL-1α, and high mobility group box 1 (HMGB1). Our understanding of pyroptosis has increased over time with an increase in research on the subject: gasdermin-mediated lytic PCD usually, but not always, requires cleavage by caspases. Moreover, new evidence suggests that pyroptosis induction in tumor cells results in a strong inflammatory response and significant cancer regression, which has stimulated great interest among scientists for its potential application in clinical cancer therapy. It's worth noting that the side effects of chemotherapy and radiotherapy can be triggered by pyroptosis. Thus, the intelligent use of pyroptosis, the double-edged sword for tumors, will enable us to understand the genesis and development of cancers and provide potential methods to develop novel anticancer drugs based on pyroptosis. Hence, in this review, we systematically summarize the molecular mechanisms of pyroptosis and provide the latest available evidence supporting the antitumor properties of pyroptosis, and provide a summary of the various antitumor medicines targeting pyroptosis signaling pathways.

To study pyroptosis-related biomarkers that are associated with the prognosis and immune microenvironment characteristics of osteosarcoma (OS). The goal is to establish a foundation for the prognosis and treatment of OS.

We retrieved transcriptome and clinical data from The Cancer Genome Atlas (TCGA) database for 88 OS patients. Using this data, we constructed a prognostic model to identify pyroptosis-related genes (PRGs) associated with OS prognosis. To further explore the biological function of these PRGs, we performed enrichment analysis. To identify pyroptosis-related long non-coding RNAs (PRLncs) associated with the prognosis of OS, we performed co-expression analysis. Subsequently, a risk prognostic model was constructed using these PRLncs to generate a risk score, termed as PRLncs-score, thereby obtaining PRLncs associated with the prognosis of OS. The accuracy of the prognostic model was verified through survival analysis, risk curve, independent prognostic analysis, receiver operating characteristic (ROC) curve, difference analysis between high- and low-risk groups, and clinical correlation analysis. And to determine whether PRLncs-score is independent prognostic factor for OS. In addition, we further conducted external and internal validation for the risk prognosis model. Further analyses of immune cell infiltration and tumor microenvironment were performed. A pyroptosis-related competitive endogenous RNA (PRceRNA) network was constructed to obtain PRceRNAs associated with the prognosis of OS and performed gene set enrichment analysis (GSEA) on PRceRNA genes.

We obtained five PRGs (CHMP4C, BAK1, GSDMA, CASP1, and CASP6) that predicted OS prognosis and seven PRLncs (AC090559.1, AP003119.2, CARD8-AS1, AL390728.4, SATB2-AS1, AL133215.2, and AC009495.3) and one PRceRNA (CARD8-AS1-hsa-miR-21-5p-IL1B) that predicted OS prognosis and indicated characteristics of the OS immune microenvironment. The PRLncs-score, in combination with other clinical features, was established as an independent prognostic factor for OS patients. Subsequent scrutiny of the tumor microenvironment and immune infiltration indicated that patients with low-PRLncs-scores were associated with reduced metastatic risk, improved survival rates, heightened levels of immune cells and stroma, and increased immune activity compared to those with high-PRLncs-scores.

The study's findings offer insight into the prognosis of OS and its immune microenvironment, and hold promise for improving early diagnosis and immunotherapy.

Skin cutaneous melanoma (SKCM) is one of the most malignant forms of skin cancer, characterized by its high metastatic potential and low cure rate in advanced stages. Despite advancements in clinical therapies, the overall cure rate for SKCM remains low due to its resistance to conventional treatments. Inflammation is associated with the activation and regulation of inflammatory responses and plays a crucial role in the immune system. It has been implicated in various physiological and pathological processes, including cancer. However, the mechanisms of inflammasome activation in SKCM remain largely unexplored. In this study, we quantified the expression level of six inflammasome-related gene sets using transcriptomic data from SKCM patients. As a result, we found that inflammasome features were closely associated with various clinical characteristics and served as a favorable prognostic factor for patients. A functional enrichment analysis revealed the oncogenic role of inflammasome features in SKCM. Unsupervised clustering was applied to identify immune clusters and inflammatory subtypes, revealing a significant overlap between immune cluster 4 and SKCM subtype 2. The CASP1, GSDMD, NLRP3, IL1B, and IL18 features could predict immune checkpoint blockade therapy response in various SKCM cohorts. In conclusion, our study highlighted the significant association between the inflammasome and cancer treatment. Understanding the role of inflammasome signaling in SKCM pathology can help identify potential therapeutic targets and improve patient prognosis.

Pyroptosis is a type of programmed cell death and plays a dual role in distinct cancers. It is elusive to evaluate the activation level of pyroptosis and to appraise the involvement of pyroptosis in the occurrence and development of diverse tumors. Accordingly, we herein established an indicator to evaluate pyroptosis related gene transcription levels based on the expression level of genes involved in pyroptosis and tried to elaborated on the association between pyroptosis and tumors across diverse tumor types. We found that pyroptosis related gene transcription levels could predict the prognosis of patients, which could act as either a favorable or a dreadful factor in diverse cancers. According to signaling pathway analyses we observed that pyroptosis played a significant role in immune regulation and tumorigenesis and had strong links with other forms of cell death. We also performed analysis on the crosstalk between pyroptosis and immune status and further investigated the predictive potential of pyroptosis level for the efficacy of immunotherapy. Lastly, we manifested that pyroptosis status could serve as a biomarker to the efficacy of chemotherapy across various cancers. In summary, this study established a quantitative indicator to evaluate pyroptosis related gene transcription levels, systematically explored the role of pyroptosis in pan-cancer. These results could provide potential research directions targeting pyroptosis, and highlighted that pyroptosis may be used to develop a novel strategy for the treatment of cancer.

Pyroptosis is a type of inflammatory cell death that is triggered by the formation of pores on the cell membrane by gasdermin (GSDM) family proteins. This process activates inflammasomes and leads to the maturation and release of proinflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-18 (IL-18). Pyroptosis, a form of programmed cell death, has been found to be associated with various biomolecules such as caspases, granzymes, non-coding RNA (lncRNA), reactive oxygen species (ROS), and NOD-like receptor protein 3 (NLRP3). These biomolecules have been shown to play a dual role in cancer by affecting cell proliferation, metastasis, and the tumor microenvironment (TME), resulting in both tumor promotion and anti-tumor effects. Recent studies have found that Oridonin (Ori) has anti-tumor effects by regulating pyroptosis through various pathways. Ori can inhibit pyroptosis by inhibiting caspase-1, which is responsible for activating pyroptosis of the canonical pathway. Additionally, Ori can inhibit pyroptosis by inhibiting NLRP3, which is responsible for activating pyroptosis of the noncanonical pathway. Interestingly, Ori can also activate pyroptosis by activating caspase-3 and caspase-8, which are responsible for activating pyroptosis of the emerging pathway; Ori has been found to be effective in inhibiting pyroptosis by blocking the action of perforin, which is responsible for facilitating the entry of granzyme into cells and activating pyroptosis. Additionally, Ori plays a crucial role in regulating pyroptosis by promoting the accumulation of ROS while inhibiting the ncRNA and NLRP3 pathways. It is worth noting that all of these pathways ultimately regulate pyroptosis by influencing the cleavage of GSDM, which is a key factor in the process. These studies concludes that Ori has extensive anti-cancer effects that are related to its potential regulatory function on pyroptosis. The paper summarizes several potential ways in which Ori participates in the regulation of pyroptosis, providing a reference for further study on the relationship between Ori, pyroptosis, and cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Many factors such as stress, lifestyle, and dietary habits are known to play a role in the initiation and progression of the disease. Herbal therapeutic agents including curcumin can hold a great potential against cancer treatment; however, their efficacy on CRC is still under investigation. Herein, we evaluated the anticancer mechanism of curcumin on four different CRC cell lines.

Cells were treated with curcumin for 24, 48 and 72 h, and IC50 doses for each cell line were calculated. Mechanistic studies were conducted with the lowest IC50 dose determined for each cell line by evaluating apoptosis and necrosis, cell division, and NLRP3-mediated pyroptosis.

Curcumin treatment significantly decreased viability while increasing the SubG1 phase in all cell lines tested, indicating apoptosis is the main programmed cell death pathway activated upon curcumin treatment in CRC. In terms of pyroptosis, components of NLRP3 inflammasome were found to be elevated in SW480 and HCT116 cell lines, although to a lesser extent in the latter, and NLRP3 inflammasome activation was not observed in LoVo and HT29 cells.

Our results reveal that while curcumin effectively induces apoptosis, its effects on NLRP3-inflammasome mediated pyroptosis vary. Our results underline the need for further research focusing on the other inflammasome complexes to confirm the differential effects of curcumin on CRC.

Chronic inflammation is now recognized as one of the major risk factors and molecular hallmarks of chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate tumorigenesis. However, the molecular mechanisms by which chronic inflammation signaling contributes to the pathogenesis of these prostate diseases are poorly understood. Previous efforts to therapeutically target the upstream (e.g., TLRs and IL1-Rs) and downstream (e.g., NF-κB subunits and cytokines) inflammatory signaling molecules in people with these conditions have been clinically ambiguous and unsatisfactory, hence fostering the recent paradigm shift towards unraveling and understanding the functional roles and clinical significance of the novel and relatively underexplored inflammatory molecules and pathways that could become potential therapeutic targets in managing prostatic diseases. In this review article, we exclusively discuss the causal and molecular drivers of prostatitis, BPH, and prostate tumorigenesis, as well as the potential impacts of microbiome dysbiosis and chronic inflammation in promoting prostate pathologies. We specifically focus on the importance of some of the underexplored druggable inflammatory molecules, by discussing how their aberrant signaling could promote prostate cancer (PCa) stemness, neuroendocrine differentiation, castration resistance, metabolic reprogramming, and immunosuppression. The potential contribution of the IL1R-TLR-IRAK-NF-κBs signaling molecules and NLR/inflammasomes in prostate pathologies, as well as the prospective benefits of selectively targeting the midstream molecules in the various inflammatory cascades, are also discussed. Though this review concentrates more on PCa, we envision that the information could be applied to other prostate diseases. In conclusion, we have underlined the molecular mechanisms and signaling pathways that may need to be targeted and/or further investigated to better understand the association between chronic inflammation and prostate diseases.

Aims: To explore whether the expression of pyroptosis-related lncRNAs makes a difference in the prognosis and antitumor immunity of cutaneous melanoma (CM) patients. Methods: A series of analyses were conducted to establish a prognostic risk model and validate its accuracy. Immune-related analyses were performed to further assess the associations among immune status, tumor microenvironment and the prognostic risk model. Results: Eight pyroptosis-related lncRNAs relevant to prognosis were ascertained and applied to establish the prognostic risk model. The low-risk group had a higher overall survival rate. Conclusion: The established prognostic risk model presents better prediction ability for the prognosis of CM patients and provides new possible therapeutic targets for CM.

Pyroptosis could regulate tumor cell trafficking, invasion, and metastasis, as well as the tumor microenvironment (TME). However, prognostic characteristics of pyroptosis-related genes (PRGs) and their effect on the progression of glioma remain insufficient.

The genetic, transcriptional, and survival data of patients with glioma used for bioinformatic analysis were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases.

Screening of two different molecular subtypes revealed that PRG variations were associated with characteristics of TME cell infiltration, clinicopathological characteristics, and prognosis of patients with glioma. After Cox regression of differentially expressed genes, a risk score for predicting overall survival (OS) and progression-free survival (PFS) were calculated. Its predictive accuracy in patients with glioma was validated. The high-risk group of PRG signature had a poorer OS than the low-risk group (training cohort, P< 0.001; validation cohort, P< 0.001). A high risk score implies more immune cell infiltration and better immunotherapy response to immune checkpoint blockers. In addition, the differential expression of three pyroptosis-pairs in tumor and normal tissues was identified. Furthermore, the risk score was significantly associated with chemotherapeutic drug sensitivity and cancer stem cell (CSC) index. Subsequently, a highly accurate nomogram was established to facilitate applicability in the preliminary clinical application of risk score.

Our findings may provide the basis for future research targeting pyroptosis in glioma and evaluation of prognosis and development of more effective immunotherapy strategies.

Metastasis is the major cause of cancer death, and the development of therapy resistance is common. The tumor microenvironment can confer chemotherapy resistance (chemoresistance), but little is known about how specific host cells influence therapy outcome. We show that chemotherapy induces neutrophil recruitment and neutrophil extracellular trap (NET) formation, which reduces therapy response in mouse models of breast cancer lung metastasis. We reveal that chemotherapy-treated cancer cells secrete IL-1β, which in turn triggers NET formation. Two NET-associated proteins are required to induce chemoresistance: integrin-αvβ1, which traps latent TGF-β, and matrix metalloproteinase 9, which cleaves and activates the trapped latent TGF-β. TGF-β activation causes cancer cells to undergo epithelial-to-mesenchymal transition and correlates with chemoresistance. Our work demonstrates that NETs regulate the activities of neighboring cells by trapping and activating cytokines and suggests that chemoresistance in the metastatic setting can be reduced or prevented by targeting the IL-1β-NET-TGF-β axis.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) is a member of a family of peptidyl-prolyl isomerases that specifically recognizes and binds phosphoproteins, catalyzing the rapid cis-trans isomerization of phosphorylated serine/threonine-proline motifs, which leads to changes in the structures and activities of the targeted proteins. Through this complex mechanism, PIN1 regulates many hallmarks of cancer including cell autonomous metabolism and the crosstalk with the cellular microenvironment. Many studies showed that PIN1 is largely overexpressed in cancer turning on a set of oncogenes and abrogating the function of tumor suppressor genes. Among these targets, recent evidence demonstrated that PIN1 is involved in lipid and glucose metabolism and accordingly, in the Warburg effect, a characteristic of tumor cells. As an orchestra master, PIN1 finely tunes the signaling pathways allowing cancer cells to adapt and take advantage from a poorly organized tumor microenvironment. In this review, we highlight the trilogy among PIN1, the tumor microenvironment and the metabolic program rewiring.

Epidemiological investigations implied that mitochondrial DNA copy number (mtDNAcn) variations could trigger predisposition to multiple cancers, but evidence regarding gastrointestinal cancers (GICs) was still uncertain. We conducted a case-cohort study within the prospective Dongfeng-Tongji cohort, including incident cases of colorectal cancer (CRC, n = 278), gastric cancer (GC, n = 138), and esophageal cancer (EC, n = 72) as well as a random subcohort (n = 1173), who were followed up from baseline to the end of 2018. We determined baseline blood mtDNAcn and associations of mtDNAcn with the GICs risks were estimated by using weighted Cox proportional hazards models. Significant U-shaped associations were observed between mtDNAcn and GICs risks. Compared to subjects within the second quartile (Q2) mtDNAcn subgroup, those within the 1st (Q1), 3rd (Q3), and 4th (Q4) quartile subgroups showed increased risks of CRC (hazard ratio [HR] [95% confidence interval, CI] = 2.27 [1.47-3.52], 1.65 [1.04-2.62], and 2.81 [1.85-4.28], respectively) and total GICs (HR [95%CI] = 1.84 [1.30-2.60], 1.47 [1.03-2.10], and 2.51 [1.82-3.47], respectively], and those within Q4 subgroup presented elevated GC and EC risks (HR [95% CI] = 2.16 [1.31-3.54] and 2.38 [1.13-5.02], respectively). Similar associations of mtDNAcn with CRC and total GICs risks remained in stratified analyzes by age, gender, smoking, and drinking status. This prospective case-cohort study showed U-shaped associations between mtDNAcn and GICs risks, but further research works are needed to uncover underlying biological mechanisms.

Interleukin (IL)-18, an interferon-γ inducer, belongs to the IL-1 family of pleiotropic pro-inflammatory factors, and IL-18 binding protein (IL-18BP) is a native antagonist of IL-18 in vivo, regulating its activity. Moreover, IL-18 exerts an influential function in host innate and adaptive immunity, and IL-18BP has elevated levels of interferon-γ in diverse cells, suggesting that IL-18BP is a negative feedback inhibitor of IL-18-mediated immunity. Similar to IL-1β, the IL-18 cytokine is produced as an indolent precursor that requires further processing into an active cytokine by caspase-1 and mediating downstream signaling pathways through MyD88. IL-18 has been implicated to play a role in psoriasis, atopic dermatitis, rosacea, and bullous pemphigoid in human inflammatory skin diseases. Currently, IL-18BP is less explored in treating inflammatory skin diseases, while IL-18BP is being tested in clinical trials for other diseases. Thereby, IL-18BP is a prospective therapeutic target.

Over the last few decades, the immune system has been steered toward eradication of cancer cells with the help of cancer immunotherapy. T cells, B cells, monocytes/macrophages, dendritic cells, T-reg cells, and natural killer (NK) cells are some of the numerous immune cell types that play a significant part in cancer cell detection and reduction of inflammation, and the antitumor response. Briefly stated, chimeric antigen receptors, adoptive transfer and immune checkpoint modulators are currently the subjects of research focus for successful immunotherapy-based treatments for a variety of cancers. This chapter discusses ongoing investigations on the mechanisms and recent developments by which receptors of immune cells especially that of lymphocytes and monocytes/macrophages regulate the detection of immune system leading to malignancies. We will also be looking into the treatment strategies based on these mechanisms.

Chronic inflammation may promote the incidence and development of neoplasms. As a pro-inflammatory death pathway, pyroptosis could induce normal cells to transform into cancerous cells, but the potential effect of pyroptosis in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study developed and evaluated a pyroptosis-related gene signature to predict the prognosis and immune status of patients with HNSCC. The gene expression, mutation information, and clinical characteristics of HNSCC were extracted from TCGA to establish a comprehensive genome database (GEO). Based on LASSO Cox regression model, nine pyroptosis-related genes (TTLL1, TRIML2, DYNC1I1, KLHL35, CAMK2N1, TNFRSF18, GLDC, SPINK5, and DKK1) were used to construct a pyroptosis-related gene signature, which had good ability to predict the prognosis of HNSCC. Furthermore, the expression of nine pyroptosis-related genes in HNSCC and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR). The potential immunotherapeutic features and drug sensitivity prediction of this signature were also explored. Because pyroptosis regulators play an important role in HNSCC development and prognoses, further exploration might assist in identifying new biomarkers and predictors of prognosis to benefit clinical identification and management.

Sarcoma is a rare mesenchymal malignant tumor. Recently, pyroptosis has been reported to be a mode of programmed cell death. Nonetheless, levels of pyroptosis-associated genes in sarcoma and its relevance to prognostic outcomes are yet to be elucidated.

Sarcoma cases were classified into two subtypes with regards to differentially expressed genes. We established a profile composed of seven genes and classified the sarcoma patients into low- and high-risk groups through least absolute shrinkage and selection operator Cox regression. Survival rate of low-risk sarcoma patients was markedly higher, relative to high-risk group (P<0.001). In combination with clinical features, the risk score was established to be an independent predictive factor for OS of sarcoma patients. Chemotherapeutic drug sensitivity response analysis found 65 drugs with higher drug sensitivity in low-risk, than in high-risk group and 14 drugs with higher drug sensitivity in the high-risk patient group, compared with low-risk patient group. In addition, functional enrichment, pathway and gene mutation of the two modules were analyzed. Finally, we used qRT-PCR to detect the expression of seven pyroptosis-related genes in tumor cells, and human skeletal muscle cells, compared with human skeletal muscle cells, PODXL2, LRRC17, GABRA3, SCUBE3 and RFLNB genes show high expression levels in tumor cells, while IGHG2 and hepatic leukemia factor show low expression levels in tumor cells.

Our research suggest that pyroptosis is closely associated with sarcoma, and these findings confirm that pyroptosis-associated seven genes have a critical role in sarcoma and are potential prognostic factors for sarcoma.

Inflammasomes are related to tumorigenesis and immune-regulation. Here, we investigated the prognostic value of the NLR family pyrin domain containing (NLRP) 1/NLRP3 inflammasome and its potential mechanisms in immune-regulation in gastric cancer (GC).

We analyzed the differential expression of NLRP1/NLRP3 between tumor and normal tissues using the Oncomine and Tumor Immune Estimate Resource (TIMER) databases. Immunohistochemistry and western blotting were used to detect NLRP1/NLRP3 protein expression in GC tissues. Correlations between NLRP1/NLRP3 expression levels and patient survival were analyzed using Kaplan-Meier survival curves. The relationships of NLRP1/NLRP3 expression and tumor-infiltrating immune cells/marker genes were assessed using the TIMER database. NLRP1/NLRP3 and immune checkpoint gene correlations were verified by single-gene co-expression analyses, and tumor immune-related pathways involving NLRP1/NLRP3 were analyzed using gene set enrichment analysis (GSEA).

Elevated NLRP1/NLRP3 expression was significantly correlated with lymph node metastasis, poor survival, immune-infiltrating cell abundances, and immune cell markers. NLRP3 showed stronger correlations with immune infiltration and the prognosis of gastric cancer. NLRP1 and NLRP3 might be involved in the same tumor immune-related pathways. Thus, high NLRP1/NLRP3 expression promotes immune cell infiltration and poor prognosis in GC. NLRP1/NLRP3, particularly NLRP3, may have important roles in immune infiltration and may serve as a prognostic biomarker for GC.

NLRP1/NLRP3, particularly NLRP3, may have important roles in immune infiltration and may serve as a prognostic biomarker for GC.