Tumor-infiltrating lymphocytes (TILs) can be used to monitor the immune response, and are important in predicting treatment responses and outcomes for various types of cancer. In this study, we evaluated the prognostic significance of CD8+ TILs and FOXP3+ TILs before and after neoadjuvant chemotherapy (NAC).
Except for patients who achieved pathological complete response, 136 breast cancer patients treated with NAC were examined. CD8+ TILs and FOXP3+ TILs in biopsy specimens and residual tumors were evaluated by immunohistochemistry. CD8+ TILs and FOXP3+ TILs status was assessed, and the rates of their changes before and after NAC were calculated.
All patients with high rates of changes in the CD8+ TILs or low rates of changes in the FOXP3+ TILs or high rates of changes in the CD8/FOXP3 ratio (CFR) had significantly better recurrence-free survival (RFS) (P = 0.006, P = 0.044, P < 0.001, respectively) and overall survival (OS) (P = 0.037, P = 0.025, P < 0.001, respectively). In multivariate analysis, rates of changes in the CD8+ TILs and rates of changes in the CFR were an independent predictor for RFS (hazard ratio (HR) = 2.304, 95% confidence interval (CI) 1.052-5.776, P = 0.036; HR = 4.663, 95% CI 2.133-11.68, P < 0.001, respectively). Pathological response was also significantly correlated with RFS (HR = 5.260, 95% CI 2.373-11.14, P < 0.001). Of the 39 patients with triple-negative breast cancer, rates of changes in the CFR were independent predictor for RFS (HR = 13.02, 95% CI 2.241-258.1, P = 0.002). Of the 78 patients with hormone receptor-positive breast cancer, rates of changes in the CFR were significantly correlated with RFS too (HR = 4.377, 95% CI 1.641-13.71, P = 0.003).
Improvement in immune microenvironment following NAC has a relationship with good outcome. In particular, rates of changes in the CFR may be a useful biomarker to predict prognosis of patients treated with NAC in all breast cancer subtypes.
Shinichiro Kashiwagi
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All authors have declared no conflicts of interest.