FIGURE 2.

The anti-tumor role of PI3K inhibitors on breast cancer with direct inhibition on cancer cell proliferation and indirect stimulation of the immune response, and potential synergy with immune checkpoint inhibition. PI3Kδ inhibitor is shown to suppress Treg function. PI3Kγ inhibitor may prevent MDSC infiltration and accumulation and polarize macrophages to the M1 phenotypes. PI3Kβ inhibition antagonizes the p110β activity required for PTEN-null tumor and targets the increased PD-L1 expression on PTEN-null tumor. PI3Kα inhibition is demonstrated to be effective at preventing tumor cell growth, especially in PIK3CA mutants, but might also be promising in PTEN-null tumor to prevent the PI3Kβ/α feedback loop.