Dapl1 controls NFATc2 activation to regulate CD8⁺ T cell exhaustion and responses in chronic infection and cancer.

ABSTRACT: CD8⁺ T cells are central mediators of immune responses against infections and cancer. Here we identified Dapl1 as a crucial regulator of CD8⁺ T cell responses to cancer and infections. Dapl1 deficiency promotes the expansion of tumour-infiltrating effector memory-like CD8⁺ T cells and prevents their functional exhaustion, coupled with increased antitumour immunity and improved efficacy of adoptive T cell therapy. Dapl1 controls activation of NFATc2, a transcription factor required for the effector function of CD8⁺ T cells. Although NFATc2 mediates induction of the immune checkpoint receptor Tim3, competent NFATc2 activation prevents functional exhaustion of CD8⁺ T cells. Interestingly, exhausted CD8⁺ T cells display attenuat

SUBMITTER: Zhu L 

PROVIDER: S-EPMC9704754 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature