Critical Role for CD103(+)/CD141(+) Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma.
Critical Role for CD103(+)/CD141(+) Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma.
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DOI：
10.1016/j.ccell.2016.06.003
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发表时间：
2016-08-08
期刊：
影响因子：
50.3
通讯作者：
Krummel MF
中科院分区：
文献类型：
--
作者：
Roberts EW;Broz ML;Binnewies M;Headley MB;Nelson AE;Wolf DM;Kaisho T;Bogunovic D;Bhardwaj N;Krummel MF
小鼠中携带CD103或人类中携带CD141的肿瘤内树突状细胞（DC）驱动肿瘤内CD8+ T细胞活化。使用多种策略，我们确定了这些DC在将肿瘤抗原运输到淋巴结（LN）中的关键作用，导致直接CD8+ T细胞刺激和抗原传递到驻留的骨髓细胞。这些效果都需要CCR 7。活体成像显示直接呈递给LN中的T细胞，并且这些细胞中特异性的CCR7缺失导致缺陷性LN T细胞引发和增加的肿瘤生长。人类肿瘤中CCR7表达水平与CD141+ DC、肿瘤内T细胞的特征和更好的临床结果相关。这项工作确定了一个正在进行的T细胞启动途径，应该用于肿瘤治疗。Roberts等人表明，小鼠中的肿瘤内CD103+树突状细胞（DC）或人类中的CD141+ DC将肿瘤抗原运输至淋巴结以引发CD8+ T细胞，这需要这些DC上的CCR 7。人类肿瘤中CCR7的高表达水平与CD141+ DC的特征和更好的临床结果相关。
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. Roberts et al. show that intratumoral CD103+ dendritic cells (DC) in mice, or CD141+ DC in humans, traffic tumor antigens to lymph nodes to prime CD8+ T cells, which requires CCR7 on these DC. High CCR7 expression level in human tumors correlates with signatures of CD141+ DC and better clinical outcomes.