Expression and Clinical Significance of Herpes Virus Entry Mediator (HVEM) in Breast Cancer
Expression and Clinical Significance of Herpes Virus Entry Mediator (HVEM) in Breast Cancer
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DOI：
10.1245/s10434-017-5924-1
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发表时间：
2017-12-01
影响因子：
3.7
通讯作者：
Tse, Gary M.
中科院分区：
文献类型：
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作者：
Tsang, Julia Y. S.;Chan, Kit-Wing;Tse, Gary M.
免疫检查点阻断目前正在浸润性乳腺癌中积极研究。鉴于免疫调节的复杂性，免疫检查点框架内的多种抑制性分子将参与肿瘤免疫逃逸。在框架内的组件的评估是一个先决条件，不仅确定额外的治疗目标和优化的免疫策略，但也了解这些分子的预后价值，我们研究了最近描述的组件，疱疹病毒进入介质（HVEM），在一个大的队列浸润性乳腺癌免疫组化，并评估其临床相关性。HVEM表达与侵袭性肿瘤特征相关，即高级别（p < 0.001）、高pT（p = 0.001）和pN分期（p = 0.008），并且最常见于人表皮生长因子受体2过表达亚型（67%）。有趣的是，已经观察到与程序性死亡配体1（p = 0.021）的负相关。HVEM对预后的影响取决于肿瘤浸润淋巴细胞（TIL）的水平，其中最差的结果发生在TIL低、HVEM阳性的肿瘤患者中。HVEM在乳腺癌的发生中起重要的致癌作用，并且也可能是肿瘤特异性靶点。
Immune checkpoint blockades are currently actively investigated in invasive breast cancers. Given the complexity of immune regulation, multiple inhibitory molecules within the immune checkpoint framework would be involved in tumor immune escape. Evaluation of the components within the framework is a prerequisite for not only identification of additional treatment targets and optimization of immunotherapeutic strategies but also understanding the prognostic value of these molecules.We examined a recently described component, herpes virus entry mediator (HVEM), in a large cohort of invasive breast cancers using immunohistochemistry, and evaluated its clinical relevance. HVEM expression was associated with aggressive tumor features, namely high grade (p < 0.001), high pT (p = 0.001) and pN stage (p = 0.008), and was most prevalently found in human epidermal growth factor receptor 2-overexpressed subtype (67%). Interestingly, a negative association with programmed death-ligand 1 (p = 0.021) has been observed. The prognostic impact of HVEM depended on the level of tumor-infiltrating lymphocytes (TILs), with the worst outcome occurring in patients with low TIL, HVEM-positive tumors.HVEM plays significant oncogenic roles in breast carcinogenesis, and may also be a tumor-specific target.