STING agonist inflames the cervical cancer immune microenvironment and overcomes anti-PD-1 therapy resistance

• DOI: 10.3389/fimmu.2024.1342647
• Publication Date: 2024-03-14T04:26:32Z
• Authors: Tianye Li; Weijiang Zhang; Mengke Niu; Yuze Wu; Xinyue Deng; Jianwei Zhou
• Keywords: Immune checkpoint

Background Cervical cancer poses a significant global threat to women’s health. However, current therapeutic interventions, such as radiotherapy, chemotherapy, surgical resection, and immune checkpoint inhibitors, face limitations in the advanced stages of disease. Given immunosuppressive microenvironment cervical cancer, it is imperative explore novel perspectives. In this regard, STING agonists have emerged promising candidates. Methods The expression profiles clinicopathological data were obtained from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) datasets. Prognostic analysis downstream genes (CCL5, CXCL9, CXCL10) infiltration conducted using Kaplan-Meier Plotter, ESTIMATE, deconvo_CIBERSOR . Single-cell RNA-seq (scRNA-seq) was evaluate potential MSA-2 treatment employing SingleR, chi-squared test, Set Enrichment Analysis (GSEA). Cellular interaction utilized CellChat package assess potentiation cellular following administration. Murine tumor models involving U14 TC-1, conducted, IF tissue subsequently status after treatment. Results Prognosis correlated with elevated genes, indicating prolonged survival reduced recurrence. These positively infiltration, influencing stromal scores, estimate scores. Specific cell populations, including CD8 + T cells, M1-type macrophages, NK follicular helper associated genes. scRNA-seq classic immune-excluded model revealed that exerts priming activating functions on vital components within TME, intensifies their intercellular communications. vivo assay ultimately demonstrated MSA-2, either standalone or combination anti-PD-1, effectively suppressed growth subcutaneous tumors. Moreover, strategy significantly augmented efficacy compared anti-PD-1 monotherapy by eliciting robust antitumor response. Conclusion This study highlights pivotal role pathway reshaping cancer. Combining inhibitors presents transformative approach, holding promise for improved prognosis. Further investigations are warranted broader landscape long-term effects