4.8 Article

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

期刊

CANCER CELL
卷 30, 期 2, 页码 324-336

出版社

CELL PRESS
DOI: 10.1016/j.ccell.2016.06.003

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资金

  1. NIH [U54 CA163123, R21CA191428]
  2. Genentech Predoctoral Research Fellowship
  3. Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award
  4. Achievement Reward for College Scientists Scholarship
  5. 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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