Fig. 2

The role of cGAS-STING pathway in anti-tumor immunity. The cGAS-STING pathway upregulates multiples steps in cancer-immunity cycle. DNA leakage not only activates STING pathway in tumor cell, but also promotes STING activation in dendritic cell by DNA uptake or cGAMP transfer. In tumor microenvironment, cGAS-STING in DC plays an important role in the cross-presentation and priming of tumor-specific CD8⁺ T cell. Tumor-derived DNA could be taken up by DC like protein antigen, resulting in the following upregulation of type I IFN. Type I IFN contributes to most biological effects of cGAS-STING pathway on immune cells. Firstly, type I IFN reinforces the cross-presentation of DC by promoting antigen retention and CD8α+ DC survival. Besides, DC cultured with type I IFN shows increased expression of CCR7 which indicates improved lymph node-homing capability. In addition, type I IFN upregulates the expression of multiple Th1 chemokines including CXCL9 and CXCL10 which is important for the homing of APC and trafficking of cytotoxic T lymphocytes. Abbreviations: cGAMP, cytosolic GMP-AMP; CTL, cytotoxic T lymphocytes; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; CXCL9, chemokine (C-X-C motif) ligand 9; IFN, interferon; MHC, major histocompatibility complex; PD-1/PD-L1, anti-programmed death-1/programmed death-ligand 1; TA, tumor antigen; TCR, T cell receptor; Treg, regulatory T cell