[PDF][PDF] Critical role for CD103+/CD141+ dendritic cells bearing CCR7 for tumor antigen trafficking and priming of T cell immunity in melanoma

EW Roberts, ML Broz, M Binnewies, MB Headley… - Cancer cell, 2016 - cell.com
EW Roberts, ML Broz, M Binnewies, MB Headley, AE Nelson, DM Wolf, T Kaisho…
Cancer cell, 2016cell.com
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 …
Summary
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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