| RRC ID |
78260
|
| Author |
Zhou W, Kawashima S, Ishino T, Kawase K, Ueda Y, Yamashita K, Watanabe T, Kawazu M, Dansako H, Suzuki Y, Nishikawa H, Inozume T, Nagasaki J, Togashi Y.
|
| Title |
Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment.
|
| Journal |
Cell Rep
|
| Abstract |
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 (TFH) cell infiltration, contributing to anti-tumor immunity. Furthermore, a part of the TFH cells in the TME exhibits cytotoxicity and directly attacks major histocompatibility complex-II-expressing tumors. TFH-like cytotoxic CD4+ T cells have high LAG-3/BLIMP1 and low TCF1 expression without self-renewal ability, whereas non-cytotoxic TFH 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 TFH-like CD4+ T cell exhaustion with helper progenitor and cytotoxic differentiated functions, mediating anti-tumor immunity orchestrally with CD8+ T cells.
|
| Volume |
43(2)
|
| Pages |
113797
|
| Published |
2024-2-15
|
| DOI |
10.1016/j.celrep.2024.113797
|
| PII |
S2211-1247(24)00125-6
|
| PMID |
38363680
|
| Resource |
| Mice |
RBRC01346 |
