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The ratio of CD8 + lymphocytes to tumor-infiltrating suppressive FOXP3 + effector regulatory T cells is associated with treatment response in invasive breast cancer

郷田 紀子 広島大学

2022.08.29

概要

Purpose
FOXP3 + and CD8 + are recognized markers of tumor-infiltrating lymphocytes (TILs) for breast cancer. FOXP3 +TILs are composed of effector Tregs (eTregs) and other subpopulations that are classified by their differences in suppressive function. In this prospective study, we evaluated Treg subpopulations and CD8 +TILs in breast cancer. Methods 84 patients with breast cancer were enrolled. Fresh TILs were extracted andTregs were classified into eTregs (CD4+FOXP3highCD45RA−), other FOXP3+ Treg subsets (naïve and non-Tregs), and total CD8+CD4− TILs using flow cytom- etry. The suppression strength of each Treg subpopulation was analyzed. The association between TIL subpopulations, clinicopathological characteristics, and response to chemotherapy was evaluated.

Results
The mean CD8/eTreg ratio value was 7.86 (interquartile range: 4.08–12.80). The proliferation function of eTregs was significantly suppressed compared with that of the other subpopulations (proliferation rates: control: 89.3%, + naiive- Treg: 64.2%, + non-Treg: 78.2% vs eTreg 1.93%; all P < 0.05). The patients with high with a high CD8 + /eTreg ratio achieved excellent pathological complete response (pCR) rate of neoadjuvant chemotherapy (90.2%) and the CD8/eTreg ratio were independent predictive factors for pCR (odds ratio:18.7(confidence interval 1.25–279) P < 0.05). A detailed assessment of the CD8/eTreg ratio for each patient who underwent NAC revealed that high CD8/eTreg ratio showed a significantly higher pCR rate compared to patients with a low CD8/FOXP3 ratio (39.6% vs 13.3, P < 0.05) in triple negative subtype patients with stromal TILs < 50%.

Conclusions
A high CD8/eTreg ratio enhances pCR rate in patients with invasive breast cancer.

Keywords
Breast cancer · Regulatory T cell · Tumor-infiltrating lymphocyte · FOXP3 · CD8 · Neoadjuvant chemotherapy

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