| First Author | Chow MT | Year | 2019 |
| Journal | Immunity | Volume | 50 |
| Issue | 6 | Pages | 1498-1512.e5 |
| PubMed ID | 31097342 | Mgi Jnum | J:282470 |
| Mgi Id | MGI:6381003 | Doi | 10.1016/j.immuni.2019.04.010 |
| Citation | Chow MT, et al. (2019) Intratumoral Activity of the CXCR3 Chemokine System Is Required for the Efficacy of Anti-PD-1 Therapy. Immunity 50(6):1498-1512.e5 |
| abstractText | Despite compelling rates of durable clinical responses to programmed cell death-1 (PD-1) blockade, advances are needed to extend these benefits to resistant tumors. We found that tumor-bearing mice deficient in the chemokine receptor CXCR3 responded poorly to anti-PD-1 treatment. CXCR3 and its ligand CXCL9 were critical for a productive CD8(+) T cell response in tumor-bearing mice treated with anti-PD-1 but were not required for the infiltration of CD8(+) T cells into tumors. The anti-PD-1-induced anti-tumor response was facilitated by CXCL9 production from intratumoral CD103(+) dendritic cells, suggesting that CXCR3 facilitates dendritic cell-T cell interactions within the tumor microenvironment. CXCR3 ligands in murine tumors and in plasma of melanoma patients were an indicator of clinical response to anti-PD-1, and their induction in non-responsive murine tumors promoted responsiveness to anti-PD-1. Our data suggest that the CXCR3 chemokine system is a biomarker for sensitivity to PD-1 blockade and that augmenting the intratumoral function of this chemokine system could improve clinical outcomes. |
