https://scholars.lib.ntu.edu.tw/handle/123456789/616299
標題: | Dapl1 controls NFATc2 activation to regulate CD8+ T cell exhaustion and responses in chronic infection and cancer | 作者: | Zhu, Lele Zhou, Xiaofei Gu, Meidi Kim, Jiseong Li, Yanchuan Chun-Jung Ko Xie, Xiaoping Gao, Tianxiao Cheng, Xuhong Sun, Shao-Cong |
關鍵字: | TRANSCRIPTION FACTOR NFAT; SUBSETS; SIGNATURE | 公開日期: | 七月-2022 | 出版社: | NATURE PORTFOLIO | 卷: | 24 | 期: | 7 | 來源出版物: | Nature cell biology | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/616299 | ISSN: | 1465-7392 1476-4679 |
DOI: | 10.1038/s41556-022-00942-8 |
顯示於: | 免疫學研究所 |
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