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Roberts, Edward W.; Broz, Miranda L.; Binnewies, Mikhail; Headley, Mark B.; Nelson, Amanda E.; Wolf, Denise M.; Kaisho, Tsuneyasu; Bogunovic, Dusan; Bhardwaj, Nina; Krummel, Matthew F.
Cancer cell, 08/2016, Letnik: 30, Številka: 2Journal Article
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. Display omitted •Tumor antigen trafficking and “painting” identify LN trafficking immune cells•CD103+ DC are critical tumor-draining antigen-presenting cells driving CD8+ T cells•CCR7 on CD103+ DC is required for tumor antigen drainage and T cell activation•CCR7 level in human melanoma correlates with T cell infiltration and patient survival 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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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