cGAS-STING 激动剂在临床前胶质母细胞瘤动物模型中的应用：肿瘤微环境调控与生存结局的系统综述

A systematic review of PubMed, Cochrane, and Embase was conducted through February 2025 following PRISMA guidelines. Studies were included if they evaluated STING agonists in live animal models of GBM and reported survival outcomes or tumor microenvironment changes. Two reviewers independently screened studies and extracted data. Risk of bias was assessed qualitatively based on study design and reporting characteristics. Given heterogeneity in models, treatments, and outcomes, results were synthesized descriptively.

Fourteen studies met the inclusion criteria, spanning synthetic and natural cyclic dinucleotides and non-cyclic STING agonists. Across diverse delivery methods, including intracranial injection, hydrogels, and nanoparticle systems, STING agonists were associated with increased CD8 + T-cell and NK cell infiltration and repolarization of tumor-associated macrophages toward pro-inflammatory phenotypes. Several studies reported prolonged survival, including long-term tumor clearance in select models. Combination therapies with immune checkpoint inhibitors or radiotherapy showed synergistic effects in some studies.

STING agonists can enhance anti-tumor immune responses and prolong survival in preclinical GBM models by promoting cytotoxic lymphocyte recruitment and remodeling the tumor-associated myeloid landscape. However, translation remains challenging due to limitations of current models, the limited clinical traction STING modulation has thus far achieved in other cancer types, incomplete understanding of cell-type-specific STING activation in the brain, and the possibility that sustained STING signaling may drive maladaptive inflammation rather than durable antitumor immunity.