Secretariat, Alumni Association, IDAC
Date Tuesday, 7 March 2023, 16:00~17:00
Room International Conference Room, Center for Smart-Aging Research, 1F (IDAC), Web
Title Novel strategy for priming immunogenicity through STING activation following MPS1 inhibition
Speaker Shunsuke Kitajima
Affiliation Department of Cell Biology, Japanese Foundation for Cancer Research
Organizer Kozo Tanaka (Department of Molecular Oncology, ext 8491)
Abstract Despite the impressive efficacy of PD-(L)1 blockade in lung cancer, specific genomic subsets promote intrinsic resistance. KRAS-LKB1 (KL) mutant lung cancers silence STING in an epigenetic manner, resulting in T cell exclusion and resistance to PD-(L)1 blockade. Here we discover that KL cells also minimize intracellular accumulation of 2’3’-cGAMP to further avoid downstream STING activation. An unbiased screen to co-opt this vulnerability reveals that transient MPS1 inhibition potently re-engages this pathway in KL cells via micronuclei generation. This strategy primarily impacts dividing cells, targets a major underlying mechanism of KL tumor immune escape, and involves pulse scheduling of inhibitors undergoing clinical development, facilitating translation into human trials.