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

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.

Keywords: 2-photon imaging; anti-tumor T cell priming; antigen presentation; antigen trafficking; dendritic cells; draining lymph node; melanoma; tumor; tumor immune response.