Cancer cell CCR2 orchestrates suppression of the adaptive immune response.

Fein, Miriam R, He, Xue-Yan, Almeida, Ana S, Bružas, Emilis, Pommier, Arnaud, Yan, Ran, Eberhardt, Anaïs, Fearon, Douglas T, Van Aelst, Linda, Wilkinson, John Erby, Dos Santos, Camila O, Egeblad, Mikala (October 2020) Cancer cell CCR2 orchestrates suppression of the adaptive immune response. Journal of Experimental Medicine, 217 (10). ISSN 0022-1007

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URL: https://www.ncbi.nlm.nih.gov/pubmed/32667673

DOI: 10.1084/jem.20181551

Abstract

C-C chemokine receptor type 2 (CCR2) is expressed on monocytes and facilitates their recruitment to tumors. Though breast cancer cells also express CCR2, its functions in these cells are unclear. We found that Ccr2 deletion in cancer cells led to reduced tumor growth and approximately twofold longer survival in an orthotopic, isograft breast cancer mouse model. Deletion of Ccr2 in cancer cells resulted in multiple alterations associated with better immune control: increased infiltration and activation of cytotoxic T lymphocytes (CTLs) and CD103+ cross-presenting dendritic cells (DCs), as well as up-regulation of MHC class I and down-regulation of checkpoint regulator PD-L1 on the cancer cells. Pharmacological or genetic targeting of CCR2 increased cancer cell sensitivity to CTLs and enabled the cancer cells to induce DC maturation toward the CD103+ subtype. Consistently, Ccr2-/- cancer cells did not induce immune suppression in Batf3-/- mice lacking CD103+ DCs. Our results establish that CCR2 signaling in cancer cells can orchestrate suppression of the immune response.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > lymphocyte organs, tissues, organelles, cell types and functions > cell types and functions > cell types > lymphocyte organs, tissues, organelles, cell types and functions > cell types and functions > cell types > lymphocyte organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent
CSHL Authors:	Fein, Miriam He, Xueyan Pommier, Arnaud Yan, Ran Eberhardt, Anais Fearon, Douglas Van Aelst, Linda Dos Santos, Camila O. Egeblad, Mikala Bruzas, Emilis
Communities:	CSHL Cancer Center Program > Cellular Communication in Cancer Program CSHL labs > Beyaz lab CSHL labs > Dos Santos lab CSHL labs > Egeblad lab CSHL labs > Fearon lab CSHL labs > Van Aelst lab School of Biological Sciences > Publications CSHL Cancer Center Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	5 October 2020
Date Deposited:	12 Aug 2020 16:33
Last Modified:	13 Feb 2024 21:17
PMCID:	PMC7537399
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/39601

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