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Piezo1 facilitates optimal T cell activation during tumor challenge.
Abiff, Muta; Alshebremi, Mohammad; Bonner, Melissa; Myers, Jay T; Kim, Byung-Gyu; Tomchuck, Suzanne L; Santin, Alicia; Kingsley, Daniel; Choi, Sung Hee; Huang, Alex Y.
Afiliación
  • Abiff M; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Alshebremi M; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Bonner M; Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.
  • Myers JT; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Kim BG; Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Tomchuck SL; Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Santin A; Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Kingsley D; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Choi SH; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Huang AY; Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Oncoimmunology ; 12(1): 2281179, 2023.
Article en En | MEDLINE | ID: mdl-38126029
ABSTRACT
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 CD4CD8 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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias / Antineoplásicos Límite: Animals Idioma: En Revista: Oncoimmunology Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias / Antineoplásicos Límite: Animals Idioma: En Revista: Oncoimmunology Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos