Immune cell activation occurs concurrently with metabolic reprogramming. As important components of the tumor microenvironment, monocytic myeloid-derived suppressor cells (M-MDSCs) are featured by their potent immunosuppressive abilities on anti-tumor effector cells. However, little is known about the contribution of metabolic adaptations to their suppressive roles. In this study, we found that tumor-infiltrating M-MDSCs had the same phenotype with splenic M-MDSCs. Compared with splenic M-MDSCs, tumor-infiltrating M-MDSCs exhibited stronger suppressive activities which was accompanied by higher glycolysis. Inhibition of glycolysis impaired the suppressive function of tumor M-MDSCs. Meanwhile, the results demonstrated that mTOR was responsible for this function regulation. mTOR inhibition by rapamycin decreased the glycolysis and reduced the suppressive activities of these cells. Furthermore, rapamycin treatment inhibited the tumor growth and reduced the percentage of M-MDSCs in 3LL tumor bearing mice. These results demonstrated that modulation of metabolism in immune cells can be an effective way to enhance anti-tumor effects.
[1]Fudan Univ, Sch Basic Med Sci, Dept Immunol, 138 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China;
[2]Fudan Univ, Biotherapy Res Ctr, Shanghai, Peoples R China;
[3]Fudan Univ, Huashan Hosp, Dept Digest Dis, Shanghai, Peoples R China;
[4]Fudan Univ, Dept Syst Biol Med, Sch Basic Med Sci, Shanghai, Peoples R China;
[5]Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China
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