Journal
CANCER CELL
Volume 30, Issue 2, Pages 324-336Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2016.06.003
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Funding
- NIH [U54 CA163123, R21CA191428]
- Genentech Predoctoral Research Fellowship
- Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award
- Achievement Reward for College Scientists Scholarship
- CRI Irvington Post-doctoral Fellowship
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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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