Enhanced radiation-induced immunogenic cell death activates chimeric antigen receptor T cells by targeting CD39 against glioblastoma.

ABSTRACT: Chimeric antigen receptor (CAR)-T cells directed to solid tumors have been less effective, due in part to the low or lost expression of specific tumor antigens. Herein, we developed a different strategy to enhance CAR-T cell persistence and efficacy by producing a multispecific CAR-T or vaccine based on immunogenic cell death (ICD). We demonstrated that ionizing radiation activates STAT1-IRF1-CD39 axis to upregulate CD39 expression to form an immunosuppressive tumor microenvironment (TME) to enhance radioresistance. CD39 blockade accumulates extracellular ATP, which activates NLRP3 inflammasome in dendritic cells via P2X7 receptor, thereby promoting radiation-induced ICD. Multispecific CAR-T cells in vitro prepared by elevated ICD suppress the growth of xenografts in nude mice. Radiation a

SUBMITTER: Sun T 

PROVIDER: S-EPMC9573869 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature