Critical Role for CD103(+)/CD141(+) Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma

携带 CCR7 的 CD103(+)/CD141(+) 树突状细胞在黑色素瘤中肿瘤抗原运输和 T 细胞免疫启动中的关键作用

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作者:Edward W Roberts, Miranda L Broz, Mikhail Binnewies, Mark B Headley, Amanda E Nelson, Denise M Wolf, Tsuneyasu Kaisho, Dusan Bogunovic, Nina Bhardwaj, Matthew F Krummel

Abstract

Intratumoral dendritic cells (DC) bearing CD103 in mice or CD141 in humans drive intratumoral CD8(+) T cell activation. Using multiple strategies, we identified a critical role for these DC in trafficking tumor antigen to lymph nodes (LN), resulting in both direct CD8(+) T cell stimulation and antigen hand-off to resident myeloid cells. These effects all required CCR7. Live imaging demonstrated direct presentation to T cells in LN, and CCR7 loss specifically in these cells resulted in defective LN T cell priming and increased tumor outgrowth. CCR7 expression levels in human tumors correlate with signatures of CD141(+) DC, intratumoral T cells, and better clinical outcomes. This work identifies an ongoing pathway to T cell priming, which should be harnessed for tumor therapies.

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