Changes in Tumor-Infiltrating Lymphocytes and Vascular Normalization in Breast Cancer Patients After Neoadjuvant Chemotherapy and Their Correlations With DFS
Changes in Tumor-Infiltrating Lymphocytes and Vascular Normalization in Breast Cancer Patients After Neoadjuvant Chemotherapy and Their Correlations With DFS
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乳腺癌患者新辅助化疗后肿瘤浸润淋巴细胞和血管正常化的变化及其与DFS的相关性
DOI：
10.3389/fonc.2019.01545
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发表时间：
2020-01-22
影响因子：
4.7
通讯作者：
Cheng, Jing
中科院分区：
文献类型：
--
作者：
Wang, Qiong;Xiang, Qun;Cheng, Jing
目的：分析乳腺癌（BC）患者新辅助化疗（NAC）后各种肿瘤浸润淋巴细胞（TIL）数量及血管正常化程度的变化，筛选预测预后的关键因素。方法：采用HE染色切片评估TILs浸润程度；免疫组化染色切片评估CD8+、CD4+、FOXP3+ Tregs的浸润以及PD-L1的表达；免疫荧光染色切片用于评估微血管密度（MVD）和微血管周细胞覆盖指数（MPI）。比较NAC前与NAC后的表达情况，并分析这些参数的变化与BC患者病理完全缓解（pCR）和DFS的相关性。结果：NAC后，pCR组中sTILs增强的患者比例显着高于非pCR组（P < 0.05）。单因素和多因素分析显示，NAC前FOXP3+ Tregs和MPI的数量与pCR相关（P < 0.05）。生存分析显示，FOXP3+ Tregs 降低的 BC 患者的 DFS 显着优于 FOXP3+ Tregs 升高的患者（P = 0.029）。原发肿瘤中的 sTIL 计数和 MPI 显着高于淋巴结（P < 0.05）。结论：NAC 后，FOXP3+ Tregs 浸润的减少与 BC 患者 DFS 的改善相关。 FOXP3+ Tregs 数量和 MPI 的变化可作为 BC 患者的预后标志物。
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.