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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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 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
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
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	5 October 2020
Date Deposited:	12 Aug 2020 16:33
Last Modified:	03 Jun 2022 14:08
PMCID:	PMC7537399
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/39601

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