# STING signaling pathway: An oasis in the glioblastoma immune desert

## TL;DR

This paper reviews how activating the STING pathway could help treat glioblastoma by boosting the immune response in an otherwise immune-resistant tumor environment.

## Contribution

The paper systematically reviews the role of STING signaling in glioblastoma and its potential for immunotherapy, offering insights into preclinical and clinical applications.

## Key findings

- STING activation can overcome the immunosuppressive tumor microenvironment in glioblastoma.
- Preclinical studies show strong antitumor effects of STING agonists in glioblastoma models.
- STING agonists may enhance immune cell infiltration and function when used in monotherapy or combination regimens.

## Abstract

Glioblastoma (GBM) is an “immune desert” tumor, characterized by a highly immunosuppressive tumor microenvironment (TME), which leads to immune evasion and resistance to immunotherapies. The stimulator of interferon (IFN) genes (STING) signaling pathway serves as a central hub for priming anti-tumor immunity by driving the production of type I IFNs. Thus, STING activation has shown promise for overcoming immunosuppressive TME and inhibiting tumor malignancies. Accumulating preclinical evidence shows that STING agonists exert strong antitumor effects across multiple GBM models. However, the diverse and complex roles of the STING signaling pathway in reshaping the GBM microenvironment have not been fully summarized or elucidated. This review provides an overview of the mechanisms underlying STING dysregulation and the regulatory effect of STING activation on immune cell infiltration, priming, and function. Moreover, STING agonist monotherapies, and their combination regimens or delivery via innovative platforms for GBM treatment, are critically appraised, highlighting their implications for future clinical translation.