| First Author | Zhu L | Year | 2022 |
| Journal | Nat Cell Biol | Volume | 24 |
| Issue | 7 | Pages | 1165-1176 |
| PubMed ID | 35773432 | Mgi Jnum | J:333979 |
| Mgi Id | MGI:7414447 | Doi | 10.1038/s41556-022-00942-8 |
| Citation | Zhu L, et al. (2022) Dapl1 controls NFATc2 activation to regulate CD8(+) T cell exhaustion and responses in chronic infection and cancer. Nat Cell Biol 24(7):1165-1176 |
| abstractText | 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. |
