| First Author | Meiser P | Year | 2023 |
| Journal | Cancer Cell | Volume | 41 |
| Issue | 8 | Pages | 1498-1515.e10 |
| PubMed ID | 37451271 | Mgi Jnum | J:346107 |
| Mgi Id | MGI:7519951 | Doi | 10.1016/j.ccell.2023.06.008 |
| Citation | Meiser P, et al. (2023) A distinct stimulatory cDC1 subpopulation amplifies CD8(+) T cell responses in tumors for protective anti-cancer immunity. Cancer Cell 41(8):1498-1515.e10 |
| abstractText | Type 1 conventional dendritic cells (cDC1) can support T cell responses within tumors but whether this determines protective versus ineffective anti-cancer immunity is poorly understood. Here, we use imaging-based deep learning to identify intratumoral cDC1-CD8(+) T cell clustering as a unique feature of protective anti-cancer immunity. These clusters form selectively in stromal tumor regions and constitute niches in which cDC1 activate TCF1(+) stem-like CD8(+) T cells. We identify a distinct population of immunostimulatory CCR7(neg) cDC1 that produce CXCL9 to promote cluster formation and cross-present tumor antigens within these niches, which is required for intratumoral CD8(+) T cell differentiation and expansion and promotes cancer immune control. Similarly, in human cancers, CCR7(neg) cDC1 interact with CD8(+) T cells in clusters and are associated with patient survival. Our findings reveal an intratumoral phase of the anti-cancer T cell response orchestrated by tumor-residing cDC1 that determines protective versus ineffective immunity and could be exploited for cancer therapy. |
