Reference - Detail
| RRC ID | 86818 |
|---|---|
| Author | Meiser P, Knolle MA, Hirschberger A, de Almeida GP, Bayerl F, Lacher S, Pedde AM, Flommersfeld S, Hönninger J, Stark L, Stögbauer F, Anton M, Wirth M, Wohlleber D, Steiger K, Buchholz VR, Wollenberg B, Zielinski CE, Braren R, Rueckert D, Knolle PA, Kaissis G, Böttcher JP. |
| Title | A distinct stimulatory cDC1 subpopulation amplifies CD8+ T cell responses in tumors for protective anti-cancer immunity. |
| Journal | Cancer Cell |
| Abstract |
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 CCR7neg 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, CCR7neg 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. |
| Volume | 41(8) |
| Pages | 1498-1515.e10 |
| Published | 2023-8-14 |
| DOI | 10.1016/j.ccell.2023.06.008 |
| PII | S1535-6108(23)00218-0 |
| PMID | 37451271 |
| MeSH | Antigens, Neoplasm CD8-Positive T-Lymphocytes* Dendritic Cells Humans Neoplasms* / therapy Receptors, CCR7 / metabolism |
| IF | 26.602 |
| Resource | |
| Mice | RBRC09485 |