| First Author | Tooley K | Year | 2024 |
| Journal | Cell Rep Med | Volume | 5 |
| Issue | 7 | Pages | 101640 |
| PubMed ID | 38959885 | Mgi Jnum | J:371155 |
| Mgi Id | MGI:8235987 | Doi | 10.1016/j.xcrm.2024.101640 |
| Citation | Tooley K, et al. (2024) Pan-cancer mapping of single CD8(+) T cell profiles reveals a TCF1:CXCR6 axis regulating CD28 co-stimulation and anti-tumor immunity. Cell Rep Med 5(7):101640 |
| abstractText | CD8(+) T cells must persist and function in diverse tumor microenvironments to exert their effects. Thus, understanding common underlying expression programs could better inform the next generation of immunotherapies. We apply a generalizable matrix factorization algorithm that recovers both shared and context-specific expression programs from diverse datasets to a single-cell RNA sequencing (scRNA-seq) compendium of 33,161 CD8(+) T cells from 132 patients with seven human cancers. Our meta-single-cell analyses uncover a pan-cancer T cell dysfunction program that predicts clinical non-response to checkpoint blockade in melanoma and highlights CXCR6 as a pan-cancer marker of chronically activated T cells. Cxcr6 is trans-activated by AP-1 and repressed by TCF1. Using mouse models, we show that Cxcr6 deletion in CD8(+) T cells increases apoptosis of PD1(+)TIM3(+) cells, dampens CD28 signaling, and compromises tumor growth control. Our study uncovers a TCF1:CXCR6 axis that counterbalances PD1-mediated suppression of CD8(+) cell responses and is essential for effective anti-tumor immunity. |
