Dissecting the Tumor Myeloid Compartment Reveals Rare Activating Antigen-Presenting Cells Critical for T Cell Immunity

被引：856

作者：

Broz, Miranda L. ^{[1
]}

Binnewies, Mikhail ^{[1
]}

Boldajipour, Bijan ^{[1
]}

Nelson, Amanda E. ^{[1
]}

Pollack, Joshua L. ^{[2
]}

Erle, David J. ^{[2
]}

Barczak, Andrea ^{[2
]}

Rosenblum, Michael D. ^{[3
]}

Daud, Adil ^{[4
]}

Barber, Diane L. ^{[5
]}

Amigorena, Sebastian ^{[7
]}

van't Veer, Laura J. ^{[6
]}

Sperling, Anne I. ^{[8
]}

Wolf, Denise M. ^{[6
]}

Krummel, Matthew F. ^{[1
]}

机构：

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

[2] Univ Calif San Francisco, Lung Biol Ctr, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Melanoma Clin Res Unit, San Francisco, CA 94143 USA

[5] Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA

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

[7] Inst Curie, INSERM, U932, F-75248 Paris 05, France

[8] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA

来源：

CANCER CELL | 2014年 / 26卷 / 05期

关键词：

GENE-EXPRESSION PROFILES; DENDRITIC CELLS; ANTITUMOR IMMUNITY; DISTINCT SUBSETS; MACROPHAGES; TISSUES;

D O I：

10.1016/j.ccell.2014.09.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

It is well understood that antigen-presenting cells (APCs) within tumors typically do not maintain cytotoxic T cell (CTL) function, despite engaging them. Across multiple mouse tumor models and human tumor biopsies, we have delineated the intratumoral dendritic cell (DC) populations as distinct from macrophage populations. Within these, CD103(+) DCs are extremely sparse and yet remarkably capable CTL stimulators. These are uniquely dependent on IRF8, Zbtb46, and Batf3 transcription factors and are generated by GM-CSF and FTL3L cytokines. Regressing tumors have higher proportions of these cells, T-cell-dependent immune clearance relies on them, and abundance of their transcripts in human tumors correlates with clinical outcome. This cell type presents opportunities for prognostic and therapeutic approaches across multiple cancer types.

引用

页码：638 / 652

页数：15

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