The cGAS-STING Pathway: A Promising Immunotherapy Target

Abstract

With the continuous development of immunotherapy, researchers have paid more attention to the specific immune regulatory mechanisms of various immune responses in different diseases. As a novel and vital innate immune signal pathway, the cGAS-STING signal pathway activated by nucleic acid substances, interplays with other immune responses, by which it participates in regulating cancer, autoimmune and inflammatory diseases, microbial and parasitic infectious diseases, and other diseases. With the exception of its role in innate immunity, the growing list of researches demonstrated expanding roles of the cGAS-STING signal pathway in bridging the innate immunity (macrophage polarization) with the adaptive immunity (T lymphocytes differentiation). Macrophages and T lymphocytes are the most representative cells of innate immunity and adaptive immunity, respectively. Their polarization or differentiation are involved in the pathogenesis and progression of various diseases. Here we mainly summarized recent advanced discoveries of how the cGAS-STING signal pathway regulated macrophages polarization and T lymphocytes differentiation in various diseases and vaccine applications, providing a promising direction for the development and clinical application of immunotherapeutic strategies for related diseases.

Immune-Related LncRNAs to Construct a Prognosis Risk-Assessment Model for Gastric Cancer

“…However, the cytosolic DNA-sensing pathway is also a double-edged sword and controversial. On one hand, the majority of researchers consider that tumor DNA activates the pathway to induce tumor-antigen presentation and activate the antitumor effector [ 35 , 36 , 37 ]; on the other hand, it releases vast inflammatory mediators to recruit M2 macrophage polarization, which we assume is what happened in our study [ 34 , 38 ].…”

Diet–Microbiota Interplay: An Emerging Player in Macrophage Plasticity and Intestinal Health

“…Therefore, pathways involved in mediating these responses are of high importance to unravel. Activation of the cyclic GMP-AMP synthase (cGAS)—stimulator of interferon genes (STING) signalling pathway, which promotes macrophage cross-priming—is reported to be crucial for bridging this link [ 20 ].…”

Immunotherapy approaches for the treatment of diffuse midline gliomas

“… 112 , 113 Not only does activating this pathway promote tumor infiltration by immune cells, but it also enhances the anti-tumoral efficacy of these cells. 114 Radiation may also promote downregulation of CD47 on the surface of tumor cells, augmenting the effect of anti-CD47 or anti-SIRPa antibody therapies. 115 However, one of the strongest rationales for combining radio- and immunotherapies is the immunosuppressive sequelae that radiation produces in the tumor environment that are optimally targeted by ICIs.…”