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

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 proinflammatory 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.

Keywords: STING agonist; cGAMP; cGAS-STING; combination therapy; immunotherapy; lung cancer.