The Hb moiety of V(Hb)@DOX effectively killed cancer cells by specifically targeting M2-type TAMs via the CD163 receptor, while the O2 released by Hb relieved cancer hypoxia and further enhanced the anti-cancer immunity by reducing the recruitment of M2-type TAMs, which synergistically reversed the ITME by down-regulating the expression of PD-L1 on cancer cells, reducing levels of immunosuppressive cytokines, increasing immunostimulant IFN-γ, enhancing CTL response, and inducing a robust memory immunity. This evidence concerns the gene CD274 and cancer.