cGAS-STING signaling in the tumor microenvironment induces myeloid cell activation and favors T cell-mediated antitumor immunity.

The cancer-immunity cycle is regulated by a series of stimulatory and inhibitory factors. The stimulator of interferon genes (STING) pathway, a key stimulator of type I interferon production, connects innate and adaptive immunity to promote antitumor responses. Using a syngeneic pancreatic tumor model, we characterized the single-cell landscape changes induced by STING stimulation. Our findings revealed that STING agonist treatment reprograms transcription across multiple cell lineages, enhances innate immune responses and activates lymphocytes, thereby promoting antitumor effects. Single-cell transcriptome sequencing identified significant increases in monocytes, neutrophils, macrophages, and CD8 T cells, indicating augmented tumor inflammation. Differential gene expression analysis highlighted upregulated genes related to immune cell effector mechanisms and antigen presentation. Functional assays confirmed the enhanced tumor killing effects induced by STING activation. These results underscore the potential of STING agonists in reprogramming the tumor microenvironment to potentiate antitumor immunity, although clinical translation remains challenging owing to pharmacokinetic limitations and potential systemic toxicity. Further research is needed to optimize STING agonist delivery and dosage for effective cancer immunotherapy.