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These cells express high levels of TNF receptor type 2 (TNFR2), but the ligand TNF\u2010\u03b1 also activates TNFR1, masking TNFR2\u2010specific function. We analyzed TNFR2 signaling using GM\u2010CSF\u2010induced MDSCs from TNFR2\u2010knockout mice and scR2agoTNF\u2010Fc, a TNFR2\u2010selective agonist. Stimulation with scR2agoTNF\u2010Fc maintained a highly suppressive monocytic subset. TNFR2 deficiency reduced MDSC\u2010mediated T\u2010cell suppression. TNFR2 activation also increased the expression of immunosuppressive effector molecules such as inducible nitric\u2010oxide synthase and interleukin\u201010. 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