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.

中文翻译：

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TIM-3调节乳腺癌中CD103 +树突状细胞的功能和对化学疗法的反应。

肿瘤内CD103 ⁺树突状细胞（DC）是抗肿瘤免疫所必需的。在这里，我们评估了CD103 ⁺ DC在乳腺癌小鼠模型中免疫调节剂的表达，并确定了TIM-3的表达作为治疗的靶标。在三阴性和管腔B型疾病模型中，抗TIM-3抗体改善了对紫杉醇化疗的反应，没有毒性证据。综合疗效为CD8 ⁺T细胞依赖性并与粒酶B表达增加有关；然而，TIM-3表达主要定位于人和鼠肿瘤中的髓样细胞。基因表达分析确定了联合治疗期间肿瘤内DC中Cxcl9的上调，并且由于CXCR3阻滞，Batf3缺乏症或Irf8缺乏症而消除了治疗功效。