| Literature DB >> 27424807 |
Edward W Roberts1, Miranda L Broz1, Mikhail Binnewies1, Mark B Headley1, Amanda E Nelson1, Denise M Wolf2, Tsuneyasu Kaisho3, Dusan Bogunovic4, Nina Bhardwaj5, Matthew F Krummel6.
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.Entities:
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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Year: 2016 PMID: 27424807 PMCID: PMC5374862 DOI: 10.1016/j.ccell.2016.06.003
Source DB: PubMed Journal: Cancer Cell ISSN: 1535-6108 Impact factor: 31.743