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

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

Author information

1
Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
2
Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
3
Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan.
4
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
5
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
6
Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA. Electronic address: matthew.krummel@ucsf.edu.

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

PMID:
27424807
PMCID:
PMC5374862
DOI:
10.1016/j.ccell.2016.06.003
[Indexed for MEDLINE]
Free PMC Article

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