T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer
T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer
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DOI：
10.4048/jbc.2018.21.e61
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发表时间：
2018-12-01
影响因子：
2.4
通讯作者：
Jeong, Jin Sook
中科院分区：
文献类型：
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作者：
Byun, Kyung Do;Hwang, Hyo Jun;Jeong, Jin Sook
目的：T细胞免疫球蛋白和粘蛋白结构域包含分子3（TIM-3）是一种新的与T细胞无能相关的免疫应答分子。人们对靶向乳腺癌免疫检查点分子，特别是三阴性乳腺癌（TNBC）的免疫检查点分子产生了极大的兴趣。本研究旨在探讨TIM-3在肿瘤浸润淋巴细胞（TIL）上的表达及其与临床病理参数和程序性死亡受体1（PD-1）/程序性死亡受体配体1（PD-L1）表达的关系，以及其预后作用。研究方法：用针对TIM-3、PD-1、PD-L1和乳腺癌相关分子标志物的抗体对从109个侵袭性导管癌类型TNBC样品产生的组织微阵列块进行免疫组织化学。它们的表达和临床病理参数以及生存分析之间的关联进行。结果：TIM-3在109例TNBC中均有表达，其中17例（51%）表达。高TIM-3与年轻患者（p=0.0101）、高TIL（p=0.0029）、高肿瘤分期（p=0.0018）、高PD-1（p = 0.0001）和高PD-L1（p= 0.0019）显著相关，并且往往与较高的组织学分级、缺乏广泛的原位成分和微钙化相关。高TIM-3表达与高PD-L1和高PD-1的组合免疫表型组显著相关（p < 0.0001）。高TIM-3显示了显著更好的无病生存率（DFS）（p
Purpose: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological parameters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. Methods: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. Results: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p = 0.0001) and high PD-L1 (p= 0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p < 0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p