| First Author | Zhou W | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 2 | Pages | 113797 |
| PubMed ID | 38363680 | Mgi Jnum | J:346098 |
| Mgi Id | MGI:7613945 | Doi | 10.1016/j.celrep.2024.113797 |
| Citation | Zhou W, et al. (2024) Stem-like progenitor and terminally differentiated T(FH)-like CD4(+) T cell exhaustion in the tumor microenvironment. Cell Rep 43(2):113797 |
| abstractText | Immune checkpoint inhibitors exert clinical efficacy against various types of cancer through reinvigoration of exhausted CD8(+) T cells that attack cancer cells directly in the tumor microenvironment (TME). Using single-cell sequencing and mouse models, we show that CXCL13, highly expressed in tumor-infiltrating exhausted CD8(+) T cells, induces CD4(+) follicular helper T (T(FH)) cell infiltration, contributing to anti-tumor immunity. Furthermore, a part of the T(FH) cells in the TME exhibits cytotoxicity and directly attacks major histocompatibility complex-II-expressing tumors. T(FH)-like cytotoxic CD4(+) T cells have high LAG-3/BLIMP1 and low TCF1 expression without self-renewal ability, whereas non-cytotoxic T(FH) cells express low LAG-3/BLIMP1 and high TCF1 with self-renewal ability, closely resembling the relationship between terminally differentiated and stem-like progenitor exhaustion in CD8(+) T cells, respectively. Our findings provide deep insights into T(FH)-like CD4(+) T cell exhaustion with helper progenitor and cytotoxic differentiated functions, mediating anti-tumor immunity orchestrally with CD8(+) T cells. |
