Identification And Functional Study Of A Novel Subset Of Myeloid Suppressor Cells (dMSC) Which Promote Tumor Metastasis And Immune Escape

Myeloid suppressor cells (MSC) are heterogeneous immature myeloid cells which are involved in the immune tolerance maintenance. To further study the subpopulations and function of MSC, we isolated MSC from spleen, lymph nodes and solid tumor mass of tumor-bearing mice. We successfully identified a new subset of MSC from tumor-infiltrating cells, which were named as differentiated MSC (dMSC) with the phenotype of Gr-1lowCD11blow, a samll size and secretion of high level IL-6, TGF-β1, VEGF, NO and PGE2. IL-6, VEGF and TGF-β1 secreted by tumor cells prompted the differentiation of dMSC from conventional MSC (cMSC). dMSC could inhibit T cell proliferation, induce T cell anergy, and induce the generation of CD4+CD25+Foxp3+ regulatory T cells. NO was the main factor derived of dMSC for the inhibition of T cell proliferation. Moreover, dMSC could induce tumor metastasis through production of MMP-9 and VEGF up-regulated by dMSC-derived IL-6. In summary, dMSC, a novel subset of MSC differentiated from cMSC under tumor microenvironment, could promote tumor immune escape and metastasis. IL-6 is critical for the differentiation of dMSC and promotion of tumor metastasis by dMSC. Therefore, our results provide new mechanistic explanation for the tumor immune escape by identifying a novel subset of MSC, and blockade of IL-6 in the control of tumor growth and metastasis.