Targeting STAT3 Abrogates Tim-3 Upregulation of Adaptive Resistance to PD-1 Blockade on Regulatory T Cells of Melanoma

Background Less than 20% of melanoma patients respond to programmed cell death-1 (PD-1) blockade immunotherapies. Thus, it is crucial understand the dynamic changes in tumor microenvironment (TME) after PD-1 blockade, for developing immunotherapy efficacy. Methods A genomic analysis was conducted by The Cancer Genome Atlas (TCGA) datasets and web platform TIMER2.0 datasets. Pathway enrichment performed using Kyoto Encyclopedia Genes Genomes (KEGG) pathway. Peripheral blood mononuclear cells (PBMCs), regulatory T (Treg) cells, B16-F10 mice were used as models. cellular molecular characteristics mechanisms Treg assessed performing gene expression studies, immunohistochemistry, RNA sequencing, flow cytometry. Results Here, we evaluate countenance immunoglobulin mucin-domain containing-3 (Tim-3), various immunosuppressive factors within tumor-infiltrated treatment with anti-PD-1 or indicator transduction activator transcription 3 (STAT3) inhibitors. Increased Tim-3 markedly observed tissues resistance patients. Targeting STAT3 significantly boosts response resistant-PD-1 therapy mouse model. Mechanistically, manifestation decreases cytokines purified from individual PBMCs murine model, limiting immunosuppression cells. Conclusions Our findings indicate that on TME STAT3-dependent, providing support a target enhancing suffering melanoma.