Format

Send to

Choose Destination
Cancer Cell. 2014 Nov 10;26(5):638-52. doi: 10.1016/j.ccell.2014.09.007. Epub 2014 Oct 16.

Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity.

Author information

1
Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
2
Lung Biology Center, University of California San Francisco, San Francisco, CA 94143, USA.
3
Department of Dermatology, University of California San Francisco, San Francisco, CA 94143, USA.
4
Melanoma Clinical Research Unit, University of California San Francisco, San Francisco, CA 94143, USA.
5
Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA 94143, USA.
6
INSERM U932, Immunity and Cancer, Institut Curie, 75248 Paris Cedex 05, France.
7
Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
8
Committee on Immunology, University of Chicago, 924 E. 57th Street, Chicago, IL 60637, USA.
9
Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA. Electronic address: matthew.krummel@ucsf.edu.

Abstract

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 FLT3L 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.

PMID:
25446897
PMCID:
PMC4254577
DOI:
10.1016/j.ccell.2014.09.007
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center