Cancer immunotherapy strategies that target the cGAS-STING pathway

Abstract

Activation of the cGAS-STING pathway by cytoplasmic DNA induces the production of Type-1 interferons. Recent advances in research suggest that the cGAS-STING pathway is involved in different parts of the cancer-immunity cycle (CIC) to promote or suppress antitumor immune responses. Combination therapy of STING agonists has made certain progress in preclinical as well as clinical trials, but the selection of combination therapy regimens remains a challenge. In this review, we summarize the role of the cGAS-STING in all aspects of CIC, and focus on the combination immunotherapy strategies of STING agonists and current unsolved challenges.

Keywords: STING; cGAS; cancer-immunity cycle; immunotherapy; tumor.

Figure 1

The cGAS-STING pathway regulates each step of the cancer-immunity cycle. Combination therapy of STING agonists can target different steps of the cancer-immunity cycle and contribute to solving immunotherapy challenges in the corresponding immune types of tumors. APC, antigen-presenting cell; PD-L1, programmed death-ligand 1; DDR, DNA damage response; VEGF, vascular endothelial growth factor; IDO, indoleamine 2,3-dioxygenase; ICIs, immune checkpoint inhibitors; CAR-T cell, chimeric antigen receptor-T cell. By Figdraw.