Piezo1 facilitates optimal T cell activation during tumor challenge
Functional effector T cells in the tumor microenvironment (TME) are critical for successful anti-tumor responses. T cell anti-tumor function is dependent on their ability to differentiate from a naïve state, infiltrate into the tumor site, and exert cytotoxic functions. The factors dictating whether...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2281179 |
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| author | muta abiff Mohammad Alshebremi Melissa Bonner Jay T. Myers Byung-Gyu Kim Suzanne L. Tomchuck Alicia Santin Daniel Kingsley Sung Hee Choi Alex Y. Huang |
| author_facet | muta abiff Mohammad Alshebremi Melissa Bonner Jay T. Myers Byung-Gyu Kim Suzanne L. Tomchuck Alicia Santin Daniel Kingsley Sung Hee Choi Alex Y. Huang |
| author_sort | muta abiff |
| collection | DOAJ |
| description | Functional effector T cells in the tumor microenvironment (TME) are critical for successful anti-tumor responses. T cell anti-tumor function is dependent on their ability to differentiate from a naïve state, infiltrate into the tumor site, and exert cytotoxic functions. The factors dictating whether a particular T cell can successfully undergo these processes during tumor challenge are not yet completely understood. Piezo1 is a mechanosensitive cation channel with high expression on both CD4+ and CD8+ T cells. Previous studies have demonstrated that Piezo1 optimizes T cell activation and restrains the CD4+ regulatory T cell (Treg) pool in vitro and under inflammatory conditions in vivo. However, little is known about the role Piezo1 plays on CD4+ and CD8+ T cells in cancer. We hypothesized that disruption of Piezo1 on T cells impairs anti-tumor immunity in vivo by hindering inflammatory T cell responses. We challenged mice with T cell Piezo1 deletion (P1KO) with tumor models dependent on T cells for immune rejection. P1KO mice had the more aggressive tumors, higher tumor growth rates and were unresponsive to immune-mediated therapeutic interventions. We observed a decreased CD4:CD8 ratio in both the secondary lymphoid organs and TME of P1KO mice that correlated inversely with tumor size. Poor CD4+ helper T cell responses underpinned the immunodeficient phenotype of P1KO mice. Wild type CD8+ T cells are sub-optimally activated in vivo with P1KO CD4+ T cells, taking on a CD25loPD-1hi phenotype. Together, our results suggest that Piezo1 optimizes T cell activation in the context of a tumor response. |
| format | Article |
| id | doaj-art-415f640137ca403bb28f890113362538 |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-415f640137ca403bb28f8901133625382025-08-20T02:50:44ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2281179Piezo1 facilitates optimal T cell activation during tumor challengemuta abiff0Mohammad Alshebremi1Melissa Bonner2Jay T. Myers3Byung-Gyu Kim4Suzanne L. Tomchuck5Alicia Santin6Daniel Kingsley7Sung Hee Choi8Alex Y. Huang9Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USADepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USADepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USAPediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USAPediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USAPediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USADepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USADepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USAPediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USADepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USAFunctional effector T cells in the tumor microenvironment (TME) are critical for successful anti-tumor responses. T cell anti-tumor function is dependent on their ability to differentiate from a naïve state, infiltrate into the tumor site, and exert cytotoxic functions. The factors dictating whether a particular T cell can successfully undergo these processes during tumor challenge are not yet completely understood. Piezo1 is a mechanosensitive cation channel with high expression on both CD4+ and CD8+ T cells. Previous studies have demonstrated that Piezo1 optimizes T cell activation and restrains the CD4+ regulatory T cell (Treg) pool in vitro and under inflammatory conditions in vivo. However, little is known about the role Piezo1 plays on CD4+ and CD8+ T cells in cancer. We hypothesized that disruption of Piezo1 on T cells impairs anti-tumor immunity in vivo by hindering inflammatory T cell responses. We challenged mice with T cell Piezo1 deletion (P1KO) with tumor models dependent on T cells for immune rejection. P1KO mice had the more aggressive tumors, higher tumor growth rates and were unresponsive to immune-mediated therapeutic interventions. We observed a decreased CD4:CD8 ratio in both the secondary lymphoid organs and TME of P1KO mice that correlated inversely with tumor size. Poor CD4+ helper T cell responses underpinned the immunodeficient phenotype of P1KO mice. Wild type CD8+ T cells are sub-optimally activated in vivo with P1KO CD4+ T cells, taking on a CD25loPD-1hi phenotype. Together, our results suggest that Piezo1 optimizes T cell activation in the context of a tumor response.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2281179Cancer immunologyPiezo1rhabdomyosarcomaT cell mechanobiology |
| spellingShingle | muta abiff Mohammad Alshebremi Melissa Bonner Jay T. Myers Byung-Gyu Kim Suzanne L. Tomchuck Alicia Santin Daniel Kingsley Sung Hee Choi Alex Y. Huang Piezo1 facilitates optimal T cell activation during tumor challenge OncoImmunology Cancer immunology Piezo1 rhabdomyosarcoma T cell mechanobiology |
| title | Piezo1 facilitates optimal T cell activation during tumor challenge |
| title_full | Piezo1 facilitates optimal T cell activation during tumor challenge |
| title_fullStr | Piezo1 facilitates optimal T cell activation during tumor challenge |
| title_full_unstemmed | Piezo1 facilitates optimal T cell activation during tumor challenge |
| title_short | Piezo1 facilitates optimal T cell activation during tumor challenge |
| title_sort | piezo1 facilitates optimal t cell activation during tumor challenge |
| topic | Cancer immunology Piezo1 rhabdomyosarcoma T cell mechanobiology |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2281179 |
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