Exploring the Role of Thioredoxin system in Cancer Immunotherapy

<b>Purpose:</b> The thioredoxin (Trx) system is integral to redox regulation and participates in several physiological processes, including tumor growth, immune response, and stem cell differentiation. We have performed a comprehensive and holistic analysis of the Trx system in tumor immunity in this study. <b>Methods:</b> A study using the Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases was conducted to determine the expression and distribution of Trx system proteins. To explore and validate the correlation between Trx system expression levels and tumor progression, GTEx and TCGA datasets were used. Western blotting was used to measure Trx system expression in lung cancer cell lines, while MTT assays were used to measure cell proliferation. The Kaplan-Meier plotter database was used to explore the association between the Trx system and survival outcome of patients in pan-cancer. GO and KEGG enrichment analyses of the Trx system were performed. Next, we analyzed how the Trx system related to immune activation. Using TIDE and TISMO databases, we predicted immunotherapy responses. <b>Results:</b> An abnormal expression of the Trx system is observed in cancer cells. Interference with the Trx system with siRNA or inhibitors significantly inhibits tumor cell growth, suggesting the Trx system is crucial to tumor growth. Through a broad cohort of different cancer types, we explored the prominent role of genes in the Trx system. The Trx system showed a relatively consistent aberrant expression in pan-cancer, correlated closely with clinical prognosis. Interestingly, the Trx system was highly correlated with the clinical prognosis in pan-cancer, as well as immunity and metabolism. The abnormal expression of the thioredoxin system was positively correlated with the expression of genes associated with immune infiltration and with a decrease in survival. The Trx system was also associated with immune response to immunotherapy. <b>Conclusion:</b> The Trx system is a good predictor of both survival and the efficacy of immunotherapy, as well as clinical prognosis.