Furthermore, two studies (22, 23) of murine models (Lewis lung carcinoma and syngeneic breast cancer) demonstrated that, only low-dose anti-VEGFR2 antibody or apatinib (a novel multi-targeted VEGFR2-TKI) could maximumly alleviate hypoxia, increase the infiltration and activation of immune cells, and eventually assist anti-PD-1 therapy to maximize the anti-tumor effect in mouse models, when compared to intermediate and high doses. The gene discussed is PDCD1; the disease is breast cancer.