Raimundo F. Araújo Júnior

FOXP3 Polymorphism and Upregulation of the CXCL12‐CXCR4‐SNAIL Axis with High Infiltration of M2TAM by STAT3/NFKB Pathways Influence the Survival of Cervical Cancer Patients

Abstract This study explores the interaction between immune and cancer cells in the tumor microenvironment (TME) of cervical carcinoma (CC), with emphasis on tumor‐associated macrophages (M2‐TAMs) and the STAT3‐NF‐κB signaling pathway. It investigates how Treg cell polymorphisms and TAM infiltration through these pathways influence overall survival (OS) in CC patients. This prospective study follows 100 CC patients from 2018 to 2023 using qRT‐PCR and immunohistochemistry on tumor samples, and flow cytometry on blood samples to evaluate immunosuppressive cytokines and Treg cell polymorphisms. High stromal CD163+204+ TAM density, mediated by STAT3/NF‐κB, correlates with biomarkers such as Ki‐67, VEGFα, and FOXP3 ( p < 0.001). XPO5 expression is associated with increased STAT3, SNAIL, and HPV 16/18 levels. FOXP3 T allele deletion and HLA‐G polymorphism in the blood of patients correlate with higher STAT3 tumor expression and elevated IL‐4 and IL‐17 blood cytokines. The CXCL12‐CXCR4 axis shows a strong association with STAT3, SNAIL in TME and blood cytokines, including IL‐6 and IL‐12. Elevated CXCL12, CXCR4, and SNAIL expression in TME significantly increases mortality risk. These findings underscore the role of M2TAM infiltration and immune modulation in tumor progression and clinical outcomes in CC.