Targeting cGAS-STING pathway for reprogramming tumor-associated macrophages to enhance anti-tumor immunotherapy.

Abstract

The cyclic GMP-AMP synthase (cGAS)-stimulator interferon genes (STING) signaling pathway plays a crucial role in activating innate and specific immunity in anti-tumor immunotherapy. As the major infiltrating cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) could be polarized into either anti-tumor M1 or pro-tumor M2 types based on various stimuli. Accordingly, targeted reprogramming TAMs to restore immune balance shows promise as an effective anti-tumor strategy. In this review, we aim to target cGAS-STING pathway for reprogramming TAMs to enhance anti-tumor immunotherapy. We investigated the double-edged sword effects of cGAS-STING in regulating TME. The regulative roles of cGAS-STING pathway in TAMs and its impact on the TME were further revealed. More importantly, several strategies of targeting cGAS-STING for reprogramming TAMs were designed for enhancing anti-tumor immunotherapy. Taken together, targeting cGAS-STING pathway for reprogramming TAMs in TME might be a promising strategy to enhance anti-tumor immunotherapy.