Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives
Abstract Pyroptosis is a distinct form of programmed cell death characterized by the rupture of the cell membrane and robust inflammatory responses. Increasing evidence suggests that pyroptosis significantly affects the tumor microenvironment and antitumor immunity by releasing damage-associated mol...
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| Format: | Article |
| Language: | English |
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BMC
2025-05-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-025-02344-4 |
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| author | Chen Huang Jiayi Li Ruiyan Wu Yangqian Li Chenliang Zhang |
| author_facet | Chen Huang Jiayi Li Ruiyan Wu Yangqian Li Chenliang Zhang |
| author_sort | Chen Huang |
| collection | DOAJ |
| description | Abstract Pyroptosis is a distinct form of programmed cell death characterized by the rupture of the cell membrane and robust inflammatory responses. Increasing evidence suggests that pyroptosis significantly affects the tumor microenvironment and antitumor immunity by releasing damage-associated molecular patterns (DAMPs) and pro-inflammatory mediators, thereby establishing it as a pivotal target in cancer immunotherapy. This review thoroughly explores the molecular mechanisms underlying pyroptosis, with a particular focus on inflammasome activation and the gasdermin family of proteins (GSDMs). It examines the role of pyroptotic cell death in reshaping the tumor immune microenvironment (TIME) involving both tumor and immune cells, and discusses recent advancements in targeting pyroptotic pathways through therapeutic strategies such as small molecule modulators, engineered nanocarriers, and combinatory treatments with immune checkpoint inhibitors. We also review recent advances and future directions in targeting pyroptosis to enhance tumor immunotherapy with immune checkpoint inhibitors, adoptive cell therapy, and tumor vaccines. This study suggested that targeting pyroptosis offers a promising avenue to amplify antitumor immune responses and surmount resistance to existing immunotherapies, potentially leading to more efficacious cancer treatments. |
| format | Article |
| id | doaj-art-57950c0ef7114d7484b3a2fd985fbbf2 |
| institution | OA Journals |
| issn | 1476-4598 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj-art-57950c0ef7114d7484b3a2fd985fbbf22025-08-20T01:47:33ZengBMCMolecular Cancer1476-45982025-05-0124113010.1186/s12943-025-02344-4Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectivesChen Huang0Jiayi Li1Ruiyan Wu2Yangqian Li3Chenliang Zhang4Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityInstitute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityWest China Hospital, Sichuan UniversityInstitute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityDivision of Abdominal Tumor Multimodality Treatment, Department of Medical Oncology, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan UniversityAbstract Pyroptosis is a distinct form of programmed cell death characterized by the rupture of the cell membrane and robust inflammatory responses. Increasing evidence suggests that pyroptosis significantly affects the tumor microenvironment and antitumor immunity by releasing damage-associated molecular patterns (DAMPs) and pro-inflammatory mediators, thereby establishing it as a pivotal target in cancer immunotherapy. This review thoroughly explores the molecular mechanisms underlying pyroptosis, with a particular focus on inflammasome activation and the gasdermin family of proteins (GSDMs). It examines the role of pyroptotic cell death in reshaping the tumor immune microenvironment (TIME) involving both tumor and immune cells, and discusses recent advancements in targeting pyroptotic pathways through therapeutic strategies such as small molecule modulators, engineered nanocarriers, and combinatory treatments with immune checkpoint inhibitors. We also review recent advances and future directions in targeting pyroptosis to enhance tumor immunotherapy with immune checkpoint inhibitors, adoptive cell therapy, and tumor vaccines. This study suggested that targeting pyroptosis offers a promising avenue to amplify antitumor immune responses and surmount resistance to existing immunotherapies, potentially leading to more efficacious cancer treatments.https://doi.org/10.1186/s12943-025-02344-4PyroptosisCancer immunotherapyGasderminTumor microenvironmentInflammatory cell deathImmune response |
| spellingShingle | Chen Huang Jiayi Li Ruiyan Wu Yangqian Li Chenliang Zhang Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives Molecular Cancer Pyroptosis Cancer immunotherapy Gasdermin Tumor microenvironment Inflammatory cell death Immune response |
| title | Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives |
| title_full | Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives |
| title_fullStr | Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives |
| title_full_unstemmed | Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives |
| title_short | Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives |
| title_sort | targeting pyroptosis for cancer immunotherapy mechanistic insights and clinical perspectives |
| topic | Pyroptosis Cancer immunotherapy Gasdermin Tumor microenvironment Inflammatory cell death Immune response |
| url | https://doi.org/10.1186/s12943-025-02344-4 |
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