Myeloid suppressor cells and immune modulation in lung cancer - PubMed (original) (raw)

Review

Myeloid suppressor cells and immune modulation in lung cancer

Minu K Srivastava et al. Immunotherapy. 2012 Mar.

Abstract

Many tumors, including lung cancers, promote immune tolerance to escape host immune surveillance and facilitate tumor growth. Tumors utilize numerous pathways to inhibit immune responses, including the elaboration of immune-suppressive mediators such as PGE2, TGF-β, IL-10, VEGF, GM-CSF, IL-6, S100A8/A9 and SCF, which recruit and/or activate myeloid-derived suppressor cells (MDSCs). MDSCs, a subset of heterogeneous bone marrow-derived hematopoietic cells, are found in the peripheral blood of cancer patients and positively correlate to malignancy. Solid tumors contain MDSCs that maintain an immune-suppressive network in the tumor microenvironment. This review will focus on the interaction of tumors with MDSCs that lead to dysregulation of antigen presentation and T-cell activities in murine tumor models. Specific genetic signatures in lung cancer modulate the activities of MDSCs and impact tumor progression. Targeting MDSCs may have a long-term antitumor benefit and is at the forefront of anticancer therapeutic strategies.

PubMed Disclaimer

Figures

Figure 1

Figure 1. Myeloid-derived suppressor cell accumulation in tumors suppresses antitumor activity

MDSCs are recruited to and expanded in the tumor through the induction/production of COX-2, PGE2, IL-6, GM-CSF, S100 proteins and snail in the tumor. T-cell activation is suppressed by MDSC-mediated deprivation of l-arginine and cysteine from the environment, the production of ROS and peroxynitrite, downregulation of CD62L and the T-cell receptor-associated ζ chain, and the induction of Tregs via MDSC-mediated IL-10 and TGF-β production. MDSCs suppress NK cell cytotoxicity and NK cell IFN-γ production, and induce tumor-associated macrophages with a type 2 phenotype. MDSC expansion and IL-10 production inhibits DC antigen presentation. Ag: Antigen; DC: Dendritic cell; MDSC: Myeloid-derived suppressor cell; ROS: Reactive oxygen species; SCF: Stem cell factor.

Similar articles

Cited by

References

    1. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162–174. Comprehensive review of myeloid-derived suppressor cells in cancer. - PMC - PubMed
    1. Sica A, Bronte V. Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest. 2007;117(5):1155–1166. - PMC - PubMed
    1. Talmadge JE. Pathways mediating the expansion and immunosuppressive activity of myeloid-derived suppressor cells and their relevance to cancer therapy. Clin Cancer Res. 2007;13(18 Pt 1):5243–5248. - PubMed
    1. Peranzoni E, Zilio S, Marigo I, et al. Myeloid-derived suppressor cell heterogeneity and subset definition. Curr Opin Immunol. 2010;22(2):238–244. - PubMed
    1. Moretta A, Bottino C, Vitale M, et al. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol. 2001;19:197–223. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources