Fig. 2
From: Cold and hot tumors: from molecular mechanisms to targeted therapy
Regulation of tumor immune efficacy by the cGAS-STING pathway. Activation of the cGAS-STING pathway in tumor cells plays a crucial role in inducing the secretion of cytokines and chemokines, thereby promoting the immune-mediated elimination of early-stage tumor cells. Additionally, tumors have the capability to produce cGAMP, which initiates the transcription of STING in neighboring cells within the tumor microenvironment (TME). Following uptake of abnormal extracellular DNA from dying tumor cells, dendritic cells (DCs) and macrophages engage directly with cGAS. This interaction results in increased expression of co-stimulatory molecules (CD80 and CD86) and MHC molecules in these immune cells, enhancing their capability to activate a cytotoxic T-cell response. By releasing type I interferons, antigen-presenting cells (APCs) augment the cytotoxic potential of natural killer (NK) cells. Furthermore, cGAMP mitigates immunosuppression by inhibiting the recruitment of M2 macrophages and myeloid-derived suppressor cells (MDSCs). Conversely, sustained activation of the STING pathway suppresses dendritic cells (DCs) while attracting myeloid-derived suppressor cells (MDSCs), thereby tilting the balance towards an immunosuppressive tumor microenvironment (TME). Moreover, the involvement of STING in stromal and endothelial cells elicits anti-tumor effects by enhancing the inflammatory milieu, attracting immune cells, and guiding tumor necrosis. The cGAS-STING signaling pathway exhibits a dual role in both promoting and inhibiting tumor growth, with its effects predominantly influenced by the intensity and duration of the stimuli. In this context, black arrows represent promotion, while black bars symbolize inhibition. This figure was created using Figdraw
