Dataset Information

Eliciting pyroptosis to fuel cancer immunotherapy: mechanisms and strategies.

ABSTRACT: Immune checkpoint blockade (ICB) therapy has recently shown promise in treating several malignancies. However, only a limited number of patients respond to this treatment, partially because of the "immune cold" condition of the tumor immune microenvironment. Pyroptosis is a type of gasdermin-mediated programmed cell death that often leads to inflammation and immune responses. Many studies on the mechanism and function of pyroptosis have led to increasing recognition of the role of pyroptosis in malignant progression and immune therapy. Pyroptosis has the potential to alter the tumor immune microenvironment by releasing tumor-associated antigens, damage-associated molecular patterns, and proinflammatory cytokines, thus leading to intratumoral inflammatory responses, stimulation of tumor-specific cytotoxic T cell infiltration, conversion of "cold" to "hot" tumors, and ultimately improving the efficacy of ICB therapy. Some cancer treatments have been shown to restore anticancer immunosurveillance through the induction of pyroptosis. Therapy promoting pyroptosis and ICB therapy may have synergistic effects in cancer treatment. This review summarizes the mechanisms and roles of pyroptosis in the tumor microenvironment and combination treatment strategies. An improved understanding of the roles of pyroptosis in tumorigenesis, immune evasion, and treatment would aid in the development of therapeutic strategies for malignancies.

SUBMITTER: Wang W

PROVIDER: S-EPMC9334758 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Eliciting pyroptosis to fuel cancer immunotherapy: mechanisms and strategies.

Wang Wuyin W Zhang Lu L Sun Zhijun Z

Cancer biology & medicine 20220701 7

Immune checkpoint blockade (ICB) therapy has recently shown promise in treating several malignancies. However, only a limited number of patients respond to this treatment, partially because of the "immune cold" condition of the tumor immune microenvironment. Pyroptosis is a type of gasdermin-mediated programmed cell death that often leads to inflammation and immune responses. Many studies on the mechanism and function of pyroptosis have led to increasing recognition of the role of pyroptosis in ...[more]

PMID: 35856558

Similar Datasets

Project description:BackgroundPyroptosis is a critical type of programmed cell death that is strongly associated with the regulation of tumor and immune cell functions. However, the role of pyroptosis in tumor progression and remodeling of the tumor microenvironment in gliomas has not been extensively studied. Thus, in this study, we aimed to establish a comprehensive pyroptosis-related signature and uncover its potential clinical application in gliomas.MethodsThe TCGA glioma cohort was obtained and divided into training and internal validation cohorts, while the CGGA glioma cohort was used as an external validation cohort. Unsupervised consensus clustering was performed to identify pyroptosis-related expression patterns. A Cox regression analysis was performed to establish a pyroptosis-related risk signature. Real-time quantitative PCR was performed to analyze the expression of signature genes in glioma tissues. Immune infiltration was analyzed and validated by immunohistochemical staining. The expression patterns of signature genes in different cell types were analyzed using single-cell RNA sequencing data. Finally, therapeutic responses to chemotherapy, immunotherapy, and potential small-molecule inhibitors were investigated.ResultsPatients with glioma were stratified into clusters 1 and 2 based on the expression patterns of pyroptosis-related genes. Cluster 2 showed a longer overall (P<0.001) and progression-free survival time (P<0.001) than Cluster 1. CD8+ T cell enrichment was observed in Cluster 1. A pyroptosis-related risk signature (PRRS) was then established. The high PRRS group showed a significantly poorer prognosis than the low PRRS group in the training cohort (P<0.001), with validation in the internal and external validation cohorts. Immunohistochemical staining demonstrated that CD8+ T cells were enriched in high PRRS glioma tissues. PRRS genes also showed cell-specific expression in tumor and immune cells. Moreover, the high PRRS risk group showed higher temozolomide sensitivity and increased response to anti-PD1 treatment in a glioblastoma immunotherapy cohort. Finally, Bcl-2 inhibitors were screened as candidates for adjunct immunotherapy of gliomas.ConclusionThe pyroptosis-related signature established in this study can be used to reliably predict clinical outcomes and immunotherapy responses in glioma patients. The correlation between the pyroptosis signature and the tumor immune microenvironment may be used to further guide the sensitization of glioma patients to immunotherapy.

Project description:The regulation of immunosuppressive microenvironments in tumors through targeted drug delivery shows promise for immunochemotherapy in bladder cancer. Drawing inspiration from stealth tactics, a nano-vehicle camouflaged with platelets (PLTs) was developed to enable precise delivery and trigger pyroptosis for tumor immunotherapy. Methods: Erdafitinib (Erda) was nano-sized and encapsulated in PLTs to construct nano-Erda@PLT. Characterization of the PLTs camouflaged nano-vehicle was conducted using Zetasizer, SEM, and confocal laser scanning microscopy. The excellent targeted delivery property of the PLTs nano-vehicle was investigated through intravital imaging, three-dimensional microspheres, and SEM. Validation of pyroptosis in bladder cancer cells via the caspase-3/GSDME pathway was performed using western blot, immunofluorescence, and ELISA tests. Immunotherapy by nano-Erda@PLT treatment in vivo was confirmed using H&E, immunohistochemical, and flow cytometry. Lastly, the side effects of nano-Erda@PLT were assessed. Results: Proteomic analysis revealed that the activation of p-selectin on platelets facilitated the identification of nano-Erda@PLT targeted therapies. Nanoscale of Erda released in response to adenosine diphosphate, facilitated intratumoral permeation. This could contribute to an upregulation of the key proteins of pyroptosis, caspase-3 and GSDME, in bladder cancer cells due to nano-Erda@PLT accumulation. Additionally, the burst release of numerous inflammatory factors may enhance the system's adaptive immune response. In a bladder cancer animal model, this treatment was found to regulate the immunosuppressive microenvironment, resulting in effective tumor immunotherapy and the induction of a long-lasting, robust immune memory. Conclusion: PLTs-camouflaged nano-vehicles enable nano-Erda-mediated tumor immunotherapy through the induction of pyroptosis. These findings introduce a novel approach in exploring nanomaterial-mediated pyroptosis for cancer immunotherapy.

Dataset Information

Eliciting pyroptosis to fuel cancer immunotherapy: mechanisms and strategies.

Publications

Eliciting pyroptosis to fuel cancer immunotherapy: mechanisms and strategies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets