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Comprehensive Pan-cancer Analysis of 33 Human Cancers Reveals the Immunotherapy Value of FOXP3

Yiyang Chen, Wan bang Zhou, Yiju Gong, Jikui Liu, Xi Ou

Background: Previous studies reported that FOXP3 is involved in the regulation of tumor microenvironment and the regulation of tumor local immunity. However, its mechanism has not been fully studied. This study aims to explore the potential relationship between FOXP3 and cancer immunotherapy in 33 human cancers.

Methods: The gene expression data and clinical characteristics of 33 cancers were retrieved from the Cancer Genome Atlas database. The immunotherapy cohort includes GSE157893, GSE67501, and IMvigor210, which come from a comprehensive gene expression database and are included in previously published studies. Analyse clinical parameters, including patient age, gender, and tumor stage to assess the prognostic value of FOXP3. At the same time, we conducted survival analysis and correlation analysis of tumor microenvironment. The correlation between FOXP3 and immunosuppressive agents and stimulants, as well as major histocompatibility complexes was also analysed. Potential pathways related to FOXP3 signalling in cancer have also been explored. In addition, the correlation between FOXP3 and two immunotherapy biomarkers (tumor mutation burden and microsatellite instability) was studied. Finally, the immunotherapy response relationship between FOXP3 and the immunotherapy cohort was explored.

Results: Among 33 cancer types, FOXP3 expression is different in different clinical groups (gender, age, and tumor stage) in certain cancers, and it also shows potential prognostic value in predicting patient survival. FOXP3 is correlated with immune cell infiltration, immunomodulatory and immunotherapy markers. In addition, low FOXP3 expression is significantly associated with certain pathways. However, no significant correlation was observed between FOXP3 and immunotherapy response.

Conclusion: This study explored the immunotherapy value of FOXP3 expression in 33 human cancers, and provided evidence and insights for the application of FOXP3 expression in tumor immunotherapy. However, considering the bioinformatics methods used in this study, the findings of the study are only preliminary, and more relevant experimental verifications are needed.