Downregulation of SLC3A2 mediates immune evasion and accelerates metastasis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a common malignancy originating from oral mucosal tissue. OSCC cells employ immune evasion strategies to avoid immune attacks, but research on inhibiting immune evasion and delaying OSCC progression is limited. This study aimed to investigate how SLC3A2 downregulation mediates immune evasion and promotes metastasis in OSCC through bioinformatics analysis and cell experiments. Gene enrichment analysis was performed using human double sulphur death-related genes from the GSEA database. Differentially expressed genes were selected from the GEO database. Diagnostic models were constructed and validated using gene expression datasets. Immune infiltration and function were analysed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Cell experiments were conducted to evaluate the impact of SLC3A2 on immune response in OSCC. Ten double sulphur death-related genes were identified, with SLC3A2 and SLC7A11 being enriched in tongue squamous cell carcinoma-related diseases. Differential expression analysis revealed five genes (SLC3A2, SLC7A11, RPN1, GYS1 and NDUFS1) of diagnostic significance. GO analysis showed enrichment in amino acid import and transmembrane transport, while KEGG pathway analysis highlighted enrichment in ferroptosis, diabetic cardiomyopathy, and Starch and sucrose metabolism. Experimental verification confirmed higher SLC3A2 expression in OSCC cells. Overexpression of SLC3A2 inhibited cell proliferation and reduced PD-1 and CTLA-4 expression. Reduced SLC3A2 expression in OSCC promotes immune evasion and tumour progression by impairing T lymphocyte function. This study provides insights into targeted regulation of SLC3A2 expression for immune response-based therapies in OSCC.