We report that the systemic administration of HDC, by targeting NOX2, rendered intratumoral MDSCs less immunosuppressive and delayed the growth of murine EL-4 lymphoma and 4T1 breast cancer and, also, that these properties of HDC translated into improved anti-tumor efficacy of antibodies against the programmed cell death receptor 1 (PD-1) and the PD-1 ligand (PD-L1) in EL-4- and MC-38-bearing mice. Here, CYBB is linked to lymphoma.