期刊
CANCER CELL
卷 33, 期 1, 页码 60-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2017.11.019
关键词
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资金
- Breast Cancer Research Foundation
- Komen Promise award
- DoD Era of Hope Expansion
- Moffitt Cancer Center's Shula Breast Cancer award
- NCI/NIH grants [R01CA15531-06, U54CA163123-05, K99CA185325-01A1, R00CA185325-02]
- NATIONAL CANCER INSTITUTE [R01CA155331, P30CA076292, K99CA185325, U54CA163123, R00CA185325] Funding Source: NIH RePORTER
Intratumoral CD103(+) dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103(+) DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8(+) T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors. Gene expression analysis identified upregulation of Cxcl9 within intratumoral DCs during combination therapy, and therapeutic efficacy was ablated by CXCR3 blockade, Batf3 deficiency, or Irf8 deficiency.
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