cGAS-STING Pathway as the Target of Immunotherapy for Lung Cancer

Abstract

Abstract: Immunotherapy has completely changed the treatment pattern of lung cancer and significantly prolonged the overall survival of patients, especially for advanced patients. However, a large number of lung cancer patients are unable to benefit from immunotherapy, which forces us to find new therapeutic targets to overcome drug resistance to immunotherapy. Cyclical GMP-AMP synthetase (cGAS) recognizes cytoplasmic DNA and promotes the formation of cyclical GMP-AMP (cGAMP), activates stimulator of interferon genes (STING), then induces the expression of varieties pro-inflammatory cytokines and chemokines, and then promotes the cross-presentation of dendritic cells (DCs) and initiates tumor-specific CD8+T cell response, showing great potential to overcome resistance and enhance antitumor immunity. In this review，we describe recent advances in the biological function，activation mode， and current applications of cGAS-STING pathway in lung cancer therapy. We also describe the mechanisms of the inactivation of cGAS-STING pathway in lung cancer cells， hoping to promote the progress of immunotherapy of lung cancer by targeting cGAS-STING pathway.