时    间：4月10日16:00

地    点：实验教学主楼822会议室

主 持 人：高  灿 教  授

报 告 人：胡  静 副教授

题    目：PI3Kγ inhibitor IM502 reshaped the immunosuppressive tumor microenvironment by regulating tumor-associated macrophages

主要内容：Tumor-associated macrophages (TAMs) promote tumor immune evasion by remodeling the tumor microenvironment (TME). Targeting TAMs with small molecules has been a promising strategy for tumor immunotherapy. We obtained a small molecule IM502, a potent modulator of TAMs, from the metabolites using the strategy of feeding Geranylhydroquinone (GHQ) to the fungi deficient in GHQ. IM502 reprogrammed the phenotype and metabolism of TAMs and decreased the immune suppressive function of mouse and human TAMs by selectively inhibiting PI3Kγ activity. Systematically administration of IM502 effectively suppressed tumor growth, metastases, and prolonged survival in different preclinical melanoma, liver, and colorectal tumor models by reshaping the TME through targeting TAMs, with increased infiltration, cytotoxic ability, and TCR repertoire of lymphocytes. Our results provide a new strategy to efficiently generate small molecule immune modulators and support the clinical development of PI3Kγ inhibitor IM502 for tumor immunotherapy.