Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment Journal Article

   

Authors:	Lesokhin, A. M.; Hohl, T. M.; Kitano, S.; Cortez, C.; Hirschhorn-Cymerman, D.; Avogadri, F.; Rizzuto, G. A.; Lazarus, J. J.; Pamer, E. G.; Houghton, A. N.; Merghoub, T.; Wolchok, J. D.
Article Title:	Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment
Abstract:	Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells that accumulate during tumor formation, facilitate immune escape, and enable tumor progression. MDSCs are important contributors to the development of an immunosuppressive tumor microenvironment that blocks the action of cytotoxic antitumor T effector cells. Heterogeneity in these cells poses a significant barrier to studying the in vivo contributions of individual MDSC subtypes. Herein, we show that granulocyte-macrophage colony stimulating factor, a cytokine critical for the numeric and functional development of MDSC populations, promotes expansion of a monocyte-derived MDSC population characterized by expression of CD11b and the chemokine receptor CCR2. Using a toxin-mediated ablation strategy to target CCR2-expressing cells, we show that these monocytic MDSCs regulate entry of activated CD8 T cells into the tumor site, thereby limiting the efficacy of immunotherapy. Our results argue that therapeutic targeting of monocytic MDSCs would enhance outcomes in immunotherapy. ©2011 AACR.
Keywords:	controlled study; protein expression; treatment outcome; nonhuman; cd8 antigen; antigen expression; cd8+ t lymphocyte; lymphocyte proliferation; animal cell; mouse; animal tissue; cancer immunotherapy; melanoma; granulocyte macrophage colony stimulating factor; interleukin 5; animal experiment; animal model; cell population; cancer inhibition; regulatory t lymphocyte; cd11b antigen; reactive oxygen metabolite; adoptive transfer; target cell; indoleamine 2,3 dioxygenase; tumor growth; lymphocytic infiltration; cytokine release; cell expansion; t lymphocyte activation; chemokine receptor ccr2; lymphocyte count; suppressor cell; inducible nitric oxide synthase; tumor microenvironment; arginase; tumor escape; catalase; interleukin 3; myeloid derived suppressor cell
Journal Title:	Cancer Research
Volume:	72
Issue:	4
ISSN:	0008-5472
Publisher:	American Association for Cancer Research
Date Published:	2012-02-15
Start Page:	876
End Page:	886
Language:	English
DOI:	10.1158/0008-5472.can-11-1792
PROVIDER:	scopus
PMCID:	PMC3288305
PUBMED:	22174368
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84857219446&partnerID=40&md5=f9e846b3cbbc128c36b6f969d55a7da5
Notes:	--- - "Export Date: 2 April 2012" - "CODEN: CNREA" - "Source: Scopus"