Abstract

Lung adenocarcinoma (LUAD) is a major public health issue. Although immune checkpoint inhibitors have been incorporated into frontline therapy strategies for LUAD, clinical responses remain limited. Using data from The Cancer Genome Atlas database, we assessed the role of stimulator of interferon genes (STING) signaling on the tumor immune microenvironment to explore promising therapeutic strategies for LUAD. The correlation between STING signaling, TME, and the overall survival of patients with LUAD was analysed utilizing data downloaded from The Cancer Genome Atlas database. The SsGSEA, CIBERSORT, and ESTIMATE algorithms were applied, and gene set enrichment analysis (GSEA) was conducted to screen Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways between patients with LUAD expressing low and high levels of STING. High STING signaling was associated with increased levels of immunoregulatory and effector molecules, cytokines, and activated CD4/CD8 T cells. GSEA revealed that the high STING group was mainly enriched in GO terms and KEGG pathways related to the immune response. Additionally, both STING signaling and activated CD8+ T cells were positively related to overall survival. Stimulation of the STING signaling pathway within the TME may be useful as a novel immunotherapeutic strategy for LUAD, indicating combination therapy with STING agonists and immune checkpoint inhibitors.

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