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

Cancer Cell. 2016 Aug 8;30(2):324-336. doi: 10.1016/j.ccell.2016.06.003. Epub 2016 Jul 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, CD / immunology
  • Antigens, Neoplasm / immunology
  • Antigens, Surface / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Movement / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Humans
  • Integrin alpha Chains / immunology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Melanoma / immunology*
  • Melanoma / pathology
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, CCR7 / immunology*

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • Antigens, Surface
  • CCR7 protein, human
  • Ccr7 protein, mouse
  • Integrin alpha Chains
  • Receptors, CCR7
  • alpha E integrins
  • blood dendritic cell antigen 3, human