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

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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.

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Data availability

All data generated or analysed during this study are included in this published article (and its supplementary information files).

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Acknowledgements

We would like to thank all the participants in this study.

Funding

We are grateful for financial support from the National Science Foundation of China (82073288, 81902143).

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Author notes

  1. Yalan Sun and Ying Wang contributed equally to this work.

Authors and Affiliations

  1. School of Basic-Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China

    Yalan Sun, Ying Wang, Fang Lu, Xianghong Zhao & Bangshun He

  2. Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China

    Yalan Sun, Ying Wang, Fang Lu, Xianghong Zhao, Zhenlin Nie & Bangshun He

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  1. Yalan Sun
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Sun, Y., Wang, Y., Lu, F. et al. The prognostic values of FOXP3+ tumor-infiltrating T cells in breast cancer: a systematic review and meta-analysis. Clin Transl Oncol 25, 1830–1843 (2023). https://doi.org/10.1007/s12094-023-03080-1

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