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

Abstract

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.

Abundance of Regulatory T Cell (Treg) as a Predictive Biomarker for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

“…However, others have challenged this notion by either showing a lack of correlation of Treg abundance with survival [ 47 ] or by showing that abundance of Treg was associated with better survival in some cancers [ 48 ], including TNBC [ 49 , 50 , 51 ]. For instance, Treg identified by IHC was associated with the efficacy of NAC in breast cancer patients [ 52 ]. Furthermore, our group and others have found that abundance of Treg in metastatic tumor was lower than that in primary tumors [ 53 , 54 ], which appears paradoxical considering metastatic tumors are far more aggressive than the primary cancer.…”

Identification and Validation of an 6-Metabolism-Related Gene Signature and Its Correlation With Immune Checkpoint in Hepatocellular Carcinoma

“…Tumor-infiltrating immune cells affect the efficacy of radiotherapy, chemotherapy, or immunotherapy, and thus the prognosis of cancer patients (30)(31)(32). We showed that GAD1, SPP1, and WFS1 were markedly positively correlated with diverse immune cells, including B cells, CD8+T cells, CD4+T cells, macrophages, neutrophils, and dendritic cells in HCC.…”

CDKN1C as a prognostic biomarker correlated with immune infiltrates and therapeutic responses in breast cancer patients

“…It is known that tumour‐infiltrating immune cells (TIICs) play a vital prognostic role in BC patients. 8 , 9 , 10 For instance, high levels of tumour‐infiltrating lymphocytes generally indicated a favourable prognosis. 11 , 12 Another breakthrough is genetic sequencing widely applied in the individualized treatment and prognosis of BC patients.…”