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Myeloid-derived suppressor cells (MDSCs) play a pivotal role in establishing an immunosuppressive tumor microenvironment (TME), yet the mechanisms underlying their functional activation remain incompletely defined. Here, we identify the Fgl2-FcγRIIB signaling axis as a critical mediator of MDSC-driven immune evasion across solid tumors. Analysis of clinical specimens revealed that Fgl2 expression is significantly elevated in tumor tissues and inversely correlates with CD8⁺ T cell infiltration, while positively associating with the accumulation of FcγRIIB⁺ MDSCs and poor patient prognosis. We demonstrate that tumor-derived exosomes (TEX) function as efficient carriers that deliver membrane-bound Fgl2 (mFgl2) to MDSCs. These exosomes are internalized by MDSCs through FcγRIIB-mediated endocytosis, leading to an enhanced immunosuppressive function characterized by upregulated arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS) expression and an increased capacity to suppress CD8⁺ T cell proliferation. Genetic ablation of FcγRIIB or antibody-mediated neutralization of Fgl2 abolished this exosome-mediated immunosuppressive programming, restoring T cell activity and impairing tumor growth in vivo. Importantly, a therapeutic strategy combining an exosome secretion inhibitor, in combination with PD-L1 blockade and MDSCs depletion, synergistically achieved potent antitumor effects. Our findings unveil a novel exosome-dependent mechanism through which tumors systemically educate MDSCs, establishing the Fgl2-FcγRIIB axis as a promising broad-spectrum target for cancer immunotherapy.