The invention pertains to methods of treating a cancer in a subject by administering to the subject a combination of an oncolytic virus and a therapy that induces depletion of tumor-induced bone marrow myeloid-derived suppressor cells of polymorphonuclear type (PMN-MDSCs). In certain preferred embodiments, the oncolytic virus is a replication incompetent modified vaccinia TianTan (MVTT) virus having a deletion of the viral M1L-K2L genes. In other preferred embodiments, the therapy that induces depletion of tumor-induced PMN-MDSCs comprises administering an antibody against Ly6G, for example 1A8. The cancer therapies of the invention can be administered in combination with one or more additional anti-cancer therapies. Preferred additional anti-cancer therapy is an immunotherapy, such as administering a check-point inhibitor.
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