The prognostic values of FOXP3+ tumor-infiltrating T cells in breast cancer: a systematic review and meta-analysis

Abstract

Background: Tumor microenvironment is infiltrated by many immune cells, of which Regulatory T (Treg) cells are usually considered as negative regulators of the immune responses. However, the effect of FOXP3⁺ (forkhead box transcription factor 3) Treg cells infiltrated into the tumor areas on the prognosis of breast cancer is controversial. This meta-analysis aimed to dissect the potential values of FOXP3⁺ tumor-infiltrating lymphocytes (TILs) as a prognosis predictor of breast cancer.

Methods: After systematic retrieval of all relevant studies, 28 eligible articles were identified for meta-analysis. Odd ratio (OR), hazard ratio (HR), and 95% confidence interval (CI) were obtained for pooled analyses of pathological complete response (pCR), overall survival (OS), and corresponding forest plots and funnel plots were plotted, respectively.

Results: Pooled results revealed that patients with higher levels of FOXP3⁺ TILs experienced better pCR (OR: 1.24, 95% CI 1.09-1.41) and OS (HR: 0.79, 95% CI 0.64-0.97). Subgroup analysis revealed that elevated FOXP3⁺ TILs were significantly associated with improved pCR (OR: 1.20, 95% CI 1.02-1.40) and OS (HR: 0.22, 95% CI 0.06-0.88) in human epidermal growth factor receptor 2 positive (HER2⁺) breast cancer patients. Furthermore, FOXP3⁺ TILs in the stromal area were statistically correlated with the favorable pCR (OR: 1.22, 95% CI 1.08-1.38) and OS (HR: 0.68, 95% CI 0.49-0.96).

Conclusions: The predictive role of FOXP3⁺ TILs in the prognosis of breast cancer is influenced by various factors such as molecular subtype of breast cancer and the location of Treg. In HER2⁺ breast cancer and triple-negative breast cancer, FOXP3⁺ TILs are associated with better pCR and OS. Additionally, FOXP3⁺ TILs in stromal represent a favourable prognosis.

Keywords: Breast cancer; FOXP3+ Treg cells; Meta-analysis; Prognosis.