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

Edward W. Roberts, Miranda L. Broz, Mikhail Binnewies, Mark B. Headley, Amanda E. Nelson, Denise M. Wolf, Tsuneyasu Kaisho, Dusan Bogunovic, Nina Bhardwaj, Matthew F. Krummel

Research output: Contribution to journalArticlepeer-review

640 Scopus citations

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 languageEnglish
Pages (from-to)324-336
Number of pages13
JournalCancer Cell
Volume30
Issue number2
DOIs
StatePublished - 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

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