CD11b+Ly6C++Ly6G- cells show distinct function in mice with chronic inflammation or tumor burden

Abstract

BackgroundS100A9 has been shown to be important for the function of so called Myeloid Derived Suppressor Cells (MDSC). Cells with a similar phenotype are also involved in pro-inflammatory processes, and we therefore wanted to investigate the gene expression and function of these cells in animals that were either subjected to chronic inflammation, or inoculated with tumors.MethodsCD11b+Ly6C++ and Ly6G+ cells were isolated from spleen, tumor tissue or inflammatory granulomas. S100A9, Arginase 1 and iNOS gene expression in the various CD11b+ cell populations was analyzed using Q-PCR. The suppressive activity of the CD11b+ cell populations from different donors was studied in co-culture experiments.ResultsS100A9 was shown to be expressed mainly in splenic CD11b+Ly6C+G+ cells both at the RNA and protein level. Arginase I and iNOS expression could be detected in both CD11b+Ly6C+Ly6G+ and CD11b+Ly6C+G-/C++G- derived from tumors or a site of chronic inflammation, but was very low in the same cell populations isolated from the spleen. CD11b+ cells isolated from mice with peritoneal chronic inflammation were able to stimulate T lymphocytes, while CD11b+ cells from mice with peritoneal tumors suppressed T cell growth.ConclusionAn identical CD11b+Ly6C++G- cell population appears to have the ability to adopt immune stimulatory or immune suppressive functions dependent on the presence of a local inflammatory or tumor microenvironment. Thus, there is a functional plasticity in the CD11b+Ly6C++G- cell population that cannot be distinguished with the current molecular markers.

Immunosuppressive and Prometastatic Functions of Myeloid-Derived Suppressive Cells Rely upon Education from Tumor-Associated B Cells

“…As such, the loss of Tregs mostly blocks 4T1 cancer metastasis without affecting primary tumor growth (15, 17). At the later stage of cancer, tBregs appear to be needed to counteract the induction of antitumor myeloid cells (8) by switching and enhancing their regulatory function. Overall, the data presented here further underscore the importance of B cells in cancer (24, 32–36) by adding for the first time the education of MDSC to a growing list of pro-tumorigenic functions, such as the inhibition of cytotoxic CD8 + T and NK cells (37), Treg conversion (38) and M1-to-M2 macrophage polarization (39, 40).…”

“…By producing GM-CSF, VEGF, TGFβ, IL-6, IL-10, IL-13 and PGE4, cancer not only drastically expands MDSC, but also evokes their regulatory function (for reviews, see ref. (1, 8, 9)) by inducing their production of reactive nitrogen and oxygen species (NO, ROS, H 2 O 2 , and peroxinitrite) through the IL4-Stat6-dependent expression of arginase 1 (Arg-1) (10) and Stat1- and Stat3-induced expression of nitric oxide synthase (iNOS) and NADPH oxidase (NOX2) (11, 12). The expansion of MDSC is often used as a criterion of increased tumor burden and metastasis (1, 13).…”

Functional characterization of myeloid‐derived suppressor cell subpopulations during the development of experimental arthritis

“…In most tumor models, the expansion of the granulocytic MDSC population was much greater than that of the monocytic subset, and interestingly, the two subpopulations used different mechanisms to suppress T‐cell function. It has been reported that identical CD11b + Ly6C ++ Ly6G − cell populations adopt immune stimulatory or immune suppressive functions when affected by local inflammation or the tumor microenvironment . Thus, further studies are needed to investigate the molecular mechanism of MDSC‐mediated effects on T cells in vitro and in vivo.…”

Mechanisms of intimate and long-distance cross-talk between glioma and myeloid cells: How to break a vicious cycle

“…Furthermore, a distinction is made between monocytic MDSCs (in mice: CD11b + Ly6G -Ly6C high ), and polymorphonuclear or granulocytic MDSCs (in mice: CD11b + Ly6G + Ly6C low ) [62]. These two subsets have been suggested to play distinct roles in cancer, infection, and autoimmunity [63][64][65]. In cancer, granulocytic MDSCs have been shown to regulate antigen-specific T-cell tolerance and non-specific suppression, whereas monocytic MDSCs mediate non-specific suppression and promote tumour angiogenesis [66].…”