Prognostic Significance of CD4+ T Cell Transcription Factors in Tumor Microenvironment: Insights from Tumor-Infiltrating Lymphocytes in Breast Cancer

The tumor microenvironment (TME) influences breast cancer progression through immune system interactions, particularly by affecting the differentiation of CD4+ T cells. This study aims to explore how the TME affects the expression of transcription factors-Foxp3, RORγt, GATA3, and T-bet-in tumor-infiltrating lymphocytes (TILs) and their implications for clinical outcomes. Forty-eight breast cancer patients were enrolled. Tumor tissues were collected, and quantitative real-time PCR was performed to assess the expression of transcription factors. Patients with positive lymphovascular invasion (LVI) and high tumor grades exhibited significantly elevated Foxp3 expression. In contrast, RORγt expression decreased in patients with advanced disease. GATA3 levels correlated positively with LVI, tumor grade and advanced tumor stages, while T-bet expression was lower in patients with positive LVI, positive lymph node and larger tumor sizes. Multivariate analysis identified RORγt as a risk factor for lymph node involvement and stage of disease, while GATA3 emerged as a protective factor. Receiver operating characteristic (ROC) analysis demonstrated GATA3's potential for late-stage detection, and RORγt as a reliable staging marker. Our findings highlight the critical role of TIL-derived transcription factors in breast cancer progression and their potential as prognostic biomarkers, emphasizing the importance of TME-mediated T cell differentiation in shaping disease outcomes.