Chemical Biology Perspectives on STING Agonists as Tumor Immunotherapy

Abstract

Stimulator of interferon genes (STING) is a crucial adaptor protein in the innate immune response. STING activation triggers cytokine secretion, including type Ⅰ interferon and initiates T cell‐mediated adaptive immunity. The activated immune system converts "cold tumors" into "hot tumors" that are highly responsive to T cells by recruiting them to the tumor microenvironment, ultimately leading to potent and long‐lasting anti‐tumor effects. Unlike most immune checkpoint inhibitors, STING agonists represent a groundbreaking class of innate immune agonists that hold great potential for effectively targeting various cancer populations and are poised to become a blockbuster in tumor immunotherapy. This review will focus on the correlation between the STING signaling pathway and tumor immunity, as well as explore the impact of STING activation on other biological processes. Ultimately, we will summarize the development and optimization of STING agonists from a medicinal chemistry perspective, evaluate their potential in cancer therapy, and identify possible challenges for future advancement.

Ultrasound -Induced Thermal Effect Enhances the Efficacy of Chemotherapy and Immunotherapy in Tumor Treatment

“… 12 , 42 , 53 Transforming “cold tumors“ with inadequate immune cell infiltration into ”hot tumors” represents a crucial strategy for augmenting the effectiveness of immune checkpoint inhibitors. 54–56 Chemotherapy can induce immunogenic cell death (ICD) and elicit the immune response, rendering it a common adjunct to PD-L1/PD-1 checkpoint blockade immunotherapy in clinical settings. 57 , 58 The infiltration of CD8 + T cells following the combination of US irradiation, chemotherapy, and immunotherapy was investigated by collecting tumor tissues for FCM analysis 7 days after treatment.…”