Inhibition of lung tumorigenesis by a small molecule CA170 targeting the immune checkpoint protein VISTA.

ABSTRACT: Expressed on cells of the myeloid and lymphoid lineages, V-domain Ig Suppressor of T cell Activation (VISTA) is an emerging target for cancer immunotherapy. Blocking VISTA activates both innate and adaptive immunity to eradicate tumors in mice. Using a tripeptide small molecule antagonist of VISTA CA170, we found that it exhibited potent anticancer efficacy on carcinogen-induced mouse lung tumorigenesis. Remarkably, lung tumor development was almost completely suppressed when CA170 was combined with an MHCII-directed KRAS peptide vaccine. Flow cytometry and single-cell RNA sequencing (scRNA-seq) revealed that CA170 increased CD8⁺ T cell infiltration and enhanced their effector functions by decreasing the tumor infiltration of myeloid-derived suppressor cells (MDSCs) and Regulato

SUBMITTER: Pan J 

PROVIDER: S-EPMC8302676 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature