| First Author | Di Pilato M | Year | 2021 |
| Journal | Cell | Volume | 184 |
| Issue | 17 | Pages | 4512-4530.e22 |
| PubMed ID | 34343496 | Mgi Jnum | J:316848 |
| Mgi Id | MGI:6757846 | Doi | 10.1016/j.cell.2021.07.015 |
| Citation | Di Pilato M, et al. (2021) CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment. Cell 184(17):4512-4530.e22 |
| abstractText | Cytotoxic T lymphocyte (CTL) responses against tumors are maintained by stem-like memory cells that self-renew but also give rise to effector-like cells. The latter gradually lose their anti-tumor activity and acquire an epigenetically fixed, hypofunctional state, leading to tumor tolerance. Here, we show that the conversion of stem-like into effector-like CTLs involves a major chemotactic reprogramming that includes the upregulation of chemokine receptor CXCR6. This receptor positions effector-like CTLs in a discrete perivascular niche of the tumor stroma that is densely occupied by CCR7(+) dendritic cells (DCs) expressing the CXCR6 ligand CXCL16. CCR7(+) DCs also express and trans-present the survival cytokine interleukin-15 (IL-15). CXCR6 expression and IL-15 trans-presentation are critical for the survival and local expansion of effector-like CTLs in the tumor microenvironment to maximize their anti-tumor activity before progressing to irreversible dysfunction. These observations reveal a cellular and molecular checkpoint that determines the magnitude and outcome of anti-tumor immune responses. |
