Critical role for CD103 + /CD141 + dendritic cells bearing CCR7 for tumor antigen trafficking and priming of T cell immunity in melanoma

Roberts, E. W. , Broz, M. L., Binnewies, M., Headley, M. B., Nelson, A. E., Wolf, D. M., Kaisho, T., Bogunovic, D., Bhardwaj, N. and Krummel, M. F. (2016) Critical role for CD103 + /CD141 + dendritic cells bearing CCR7 for tumor antigen trafficking and priming of T cell immunity in melanoma. Cancer Cell, 30(2), pp. 324-336. (doi: 10.1016/j.ccell.2016.06.003) (PMID:27424807) (PMCID:PMC5374862)

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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.

Item Type:Articles
Additional Information:This work was supported by NIH grant U54 CA163123 and R21CA191428. M.L.B. was supported by the Genentech Predoctoral Research Fellowship, the Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award, and the Achievement Reward for College Scientists Scholarship. E.W.R. was supported by the CRI Irvington Post doctoral Fellowship.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Roberts, Dr Ed
Authors: Roberts, E. W., Broz, M. L., Binnewies, M., Headley, M. B., Nelson, A. E., Wolf, D. M., Kaisho, T., Bogunovic, D., Bhardwaj, N., and Krummel, M. F.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cancer Cell
Publisher:Elsevier (Cell Press)
ISSN:1535-6108
ISSN (Online):1878-3686
Published Online:14 July 2016

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