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.
Original language | English |
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Pages (from-to) | 324-336 |
Number of pages | 13 |
Journal | Cancer Cell |
Volume | 30 |
Issue number | 2 |
DOIs | |
State | Published - 8 Aug 2016 |
Keywords
- 2-photon imaging
- anti-tumor T cell priming
- antigen presentation
- antigen trafficking
- dendritic cells
- draining lymph node
- melanoma
- tumor
- tumor immune response