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

被引：751

作者：

Roberts, Edward W. ^{[1
]}

Broz, Miranda L. ^{[1
,6
]}

Binnewies, Mikhail ^{[1
]}

Headley, Mark B. ^{[1
]}

Nelson, Amanda E. ^{[1
]}

Wolf, Denise M. ^{[2
]}

Kaisho, Tsuneyasu ^{[3
]}

Bogunovic, Dusan ^{[4
]}

Bhardwaj, Nina ^{[5
]}

Krummel, Matthew F. ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Pathol, 513 Parnassus Ave, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA

[3] Wakayama Med Univ, Inst Adv Med, Wakayama 6418509, Japan

[4] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA

[6] Precis Immune Inc, 953 Indiana St, San Francisco, CA 94107 USA

来源：

CANCER CELL | 2016年 / 30卷 / 02期

关键词：

INFILTRATING LYMPHOCYTES; CHEMOKINE RECEPTOR; REPORTER MOUSE; LYMPH-NODE; MICROENVIRONMENT; IDENTIFICATION; IMMUNOTHERAPY; REJECTION; MIGRATION; SURVIVAL;

D O I：

10.1016/j.ccell.2016.06.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：324 / 336

页数：13

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