Additional Relevant Details  The paper, entitled "PI3K-gamma is a molecular switch that controls immune suppression,"1 describes research showing that targeting macrophage signaling pathways by inhibiting phosphoinositide-3-kinase (PI3K)-gamma may open the possibility to further improving and refining emerging immunotherapies that boost the body's own abilities to fight a range of diseases, including cancer. Infinity is conducting a Phase 1 clinical study of IPI-549, an orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. IPI-549 is the only PI3K-gamma inhibitor in clinical development.
When confronted by pathogens, injury or disease, the initial response of the body's immune system comes in the form of macrophages, a type of white blood cell that express pro-inflammatory proteins called cytokines that, in turn, activate T cells, another immune cell, to attack the health threat. The macrophages then switch gears to express other cytokines that dampen T cell activation, stimulating tissue repair. In cancer, highly abundant macrophages express anti-inflammatory cytokines that induce immune suppression, leading to enhanced tumor growth.In the Nature paper, researchers pinpoint a key, suspected player: an enzyme in macrophages called PI3K-gamma. In mouse studies, they found that macrophage PI3K-gamma signaling promotes immune suppression by inhibiting activation of anti-tumor T cells. Blocking PI3K-gamma activated the immune response and significantly suppressed growth of implanted tumors in animal models. It also boosted sensitivity of some tumors to existing anti-cancer drugs and synergized with existing immune therapy to eradicate tumors. Researchers also identified a molecular signature of immune suppression and response in mice and cancer patients that may be used to track the effectiveness of immune therapy.