Impact of Stimulator of Interferon Genes (STING) Signaling on the Tumor Immune Microenvironment

Abstract

Lung adenocarcinoma (LUAD), the most prevalent histologic subtype of NSCLC, is one of the most fatal malignancies. Despite the weighted effect of stimulator of interferon genes (STING) signaling on innate and adaptive immunity, understanding its dynamic modulation and tumor microenvironment (TME) in LUAD poses a challenge. Herein, we investigated the correlation between STING signaling, TME, and the overall survival of LUAD patients utilizing data from The Cancer Genome Atlas (TCGA). SsGSEA, CIBERSORT, and ESTIMATE algorithms were applied before gene set enrichment analysis (GSEA) was used to screen Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways between low and high STING groups of LUAD. High STING signaling demonstrated increased levels of immunoregulatory and effector molecules, cytokines, and activated CD4/CD8 T cells. GSEA revealed that the high STING group from the LUAD cohort were mainly enriched in GO terms and KEGG pathways related to immune response. Additionally, both STING signaling and activated CD8+ T cells were positively related to overall survival. Our findings suggest the stimulation of the STING signaling pathway within the TME as a novel immunotherapeutic strategy for LUAD, indicating the potential combination therapy of STING agonists and immune checkpoint inhibitors. Funding Statement: This study was supported by the China Scholarship Council (grant number: 201806325017 and 201906240104). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Lung Cancer Center, West China Hospital of Sichuan University gave ethical approval for the study.