Kinase Inhibitors’ Effects on Innate Immunity in Solid Cancers

SIMPLE SUMMARY: In this review, we evaluate the updated data of the immunological effects of kinase inhibitors on the innate immune system and provide an in-depth analysis of the underlying mechanisms. We also discuss how this immunological effect can be harnessed to improve cancer treatment and highlight recent successes, such as the combination with anti-tumor immunotherapy. Last, we explore novel kinase targets and the incorporation of them with targeted drug delivery techniques as promising research areas. ABSTRACT: Innate immune cells constitute a plastic and heterogeneous cell population of the tumor microenvironment. Because of their high tumor infiltration and close interaction with resident tumor cells, they are compelling targets for anti-cancer therapy through either ablation or functionally reprogramming. Kinase inhibitors (KIs) that target aberrant signaling pathways in tumor proliferation and angiogenesis have been shown to have additional immunological effects on myeloid cells that may contribute to a protective antitumor immune response. However, in patients with malignancies, these effects are poorly described, warranting meticulous research to identify KIs’ optimal immunomodulatory effect to support developing targeted and more effective immunotherapy. As many of these KIs are currently in clinical trials awaiting approval for the treatment of several types of solid cancer, we evaluate here the information on this drug class’s immunological effects and how such mechanisms can be harnessed to improve combined treatment regimens in cancer.