cGAS-STING activation promotes innate and adaptive immunity crosstalk and enhances anti-tumor response

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, bridges innate and adaptive immunity to promote anti-tumor 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, boosting innate immune responses and lymphocyte activation, thereby enhancing tumor killing. 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 that STING activation enhances T cell-mediated tumor killing through myeloid cell activation. These results underscore the potential of STING agonists in reprogramming the tumor microenvironment to potentiate anti-tumor immunity, although clinical translation remains challenging due to pharmacokinetic limitations and potential systemic toxicity. Further research is needed to optimize STING agonist delivery and dosage for effective cancer immunotherapy.