期刊
IMMUNITY
卷 50, 期 6, 页码 1498-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2019.04.010
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类别
资金
- National Institutes of Health [AI112521, CA204028, AR043369, CA222871, CA163222]
- Cancer Research Institute
- American Association Cancer Research Genentech Immuno-oncology Research Fellowship [17-40-18-CHOW]
- MGH Tosteson and Fund for Medical Discovery Postdoctoral Fellowship Awards
- American Association Cancer Research Basic Science Fellowships Program [18-40-01-OZGA]
- Swiss National Science Foundation Early Postdoctoral Mobility Award
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Melanoma Research Alliance
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 micro-environment. 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.
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