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Objective:  Changes in the number of various tumor-infiltrating lymphocytes (TILs) and degrees of vascular normalization in breast cancer (BC) patients after neoadjuvant chemotherapy (NAC) were analyzed to screen key factors that can predict the prognosis.   Methods:  HE-stained sections were used to assess the degree of TILs infiltration; immunohistochemically stained sections were used to assess the infiltration of CD8+, CD4+, FOXP3+ Tregs and the expression of PD-L1; immunofluorescence-stained sections were used to assess the microvessel density (MVD) and microvessel pericyte coverage index (MPI). The expression of them before NAC were compared with those after NAC, and correlations between changes in these parameters and the pathological complete remission (pCR) and DFS of BC patients were analyzed.   Results:  After NAC, the percentage of patients with enhanced sTILs in the pCR group was significantly higher than that in the Non-pCR group ( P  < 0.05). Univariate and multivariate analyses showed that the number of FOXP3+ Tregs and MPI before NAC were correlated with pCR ( P  < 0.05). Survival analysis showed that the DFS of BC patients with reduced FOXP3+ Tregs was significantly better than that of patients with elevated FOXP3+ Tregs ( P  = 0.029). The sTILs count and MPI were significantly higher in primary tumors than lymph nodes ( P  < 0.05).   Conclusion:  After NAC, the reduced infiltration of FOXP3+ Tregs was correlated with an improvement in DFS in BC patients. Changes in the number of FOXP3+ Tregs and the MPI may be used as prognostic markers for BC patients.

frontiers in oncology

Changes in Tumor-Infiltrating Lymphocytes and Vascular Normalization in Breast Cancer Patients After Neoadjuvant Chemotherapy and Their Correlations With DFS