@article{42025d1d32524c4e993588264dac1066,
title = "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 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.",
author = "Lele Zhu and Xiaofei Zhou and Meidi Gu and Jiseong Kim and Yanchuan Li and Ko, {Chun Jung} and Xiaoping Xie and Tianxiao Gao and Xuhong Cheng and Sun, {Shao Cong}",
note = "Funding Information: We thank J. P. B. Viola for NFAT expression vectors, E. J. Wherry for LCMV clone 13 and the Mutant Mouse Resource & Research Centers for Nfatc2-KO mice. We thank the Genetically Engineered Mouse Facility as well as the flow cytometry, sequencing and microarray, and animal facilities of the shared resources at The MD Anderson Cancer Center, supported by the NIH/NCI Cancer Center Support Grant (CCSG) P30CA016672. The Advanced Technology Genomics Core (ATGC) is supported by grant no. CA016672 (ATGC) and NIH grant no. 1S10OD024977-01. This study was supported by a grant from the National Institutes of Health (grant no. AI64639 to S.-C.S.). T.G. was a visiting student supported by a scholarship from the China Scholarship Council (grant no. 201906380080). Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2022",
month = jul,
doi = "10.1038/s41556-022-00942-8",
language = "English (US)",
volume = "24",
pages = "1165--1176",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Research",
number = "7",
}