Dapl1 控制 NFATc2 激活以调节 CD8(+) T 细胞耗竭及慢性感染和癌症中的应答

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 attenuated NFATc2 activation due to Tim3-mediated feedback inhibition; Dapl1 deletion rescues NFATc2 activation and thereby prevents dysfunction of exhausted CD8 + T cells in chronic infection and cancer.

These findings establish Dapl1 as a crucial regulator of CD8 + T cell immunity and a potential target for cancer immunotherapy.