Expression of soluble CD27 in extranodal natural killer/T-cell lymphoma, nasal type: potential as a biomarker for diagnosis and CD27/CD70-targeted therapy
Expression of soluble CD27 in extranodal natural killer/T-cell lymphoma, nasal type: potential as a biomarker for diagnosis and CD27/CD70-targeted therapy
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可溶性 CD27 在结外自然杀伤/T 细胞淋巴瘤（鼻型）中的表达：作为诊断和 CD27/CD70 靶向治疗的生物标志物的潜力
DOI：
10.1007/s00262-023-03394-7
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Hayashi T
中科院分区：
文献类型：
--
作者：
Nagato T;Komatsuda H;Hayashi R;Takahara M;Kishibe Kan;Yasuda Shunsuke;Yajima Yuki;Kosaka Akemi;Ohkuri Takayuki;Oikawa Kensuke;Harabuchi Shohei;Kono Michihisa;Yamaki Hidekiyo;Wakisaka Risa;Hirata-Nozaki Yui;Ohara Kenzo;Kumai Takumi;Katada Akihiro;Hayashi T
CD27及其配体CD70与肿瘤淋巴细胞的结合被认为介导了CD70阳性恶性肿瘤患者的肿瘤免疫逃避和血清可溶性CD27 （sCD27）水平的升高。我们之前发现CD70在结外自然杀伤/ t细胞淋巴瘤鼻型（ENKL）中表达，这是一种与eb病毒（EBV）相关的恶性肿瘤。然而，对于ENKL的血清sCD27表达及其与临床特征的关系以及CD27/CD70相互作用知之甚少。在本研究中，我们发现ENKL患者血清sCD27显著升高。血清sCD27水平为区分ENKL患者和健康受试者提供了极好的诊断准确性，与其他诊断标志物（乳酸脱氢酶、可溶性白细胞介素-2受体和EBV-DNA）水平呈正相关，并在治疗后显著下降。血清sCD27水平升高也与ENKL患者的晚期临床阶段显著相关，且往往与较短的生存期相对应。免疫组化提示cd27阳性肿瘤浸润性免疫细胞与cd70阳性淋巴瘤细胞相邻存在。此外，CD70阳性ENKL患者血清sCD27水平显著高于CD70阴性ENKL患者，提示肿瘤内CD27/CD70相互作用促进血清中sCD27的释放。此外，ebv编码的癌蛋白潜伏膜蛋白1上调了ENKL细胞中CD70的表达。我们的研究结果表明，sCD27可以作为一种新的诊断性生物标志物，也可以通过预测ENKL中肿瘤内CD70表达和CD27/CD70相互作用来评估CD27/CD70靶向治疗的适用性。
The engagement of CD27 on lymphocytes with its ligand, CD70, on tumors is believed to mediate tumor immune evasion and the elevation of serum soluble CD27 (sCD27) levels in patients with CD70-positive malignancies. We previously showed that CD70 is expressed in extranodal natural killer/T-cell lymphoma, nasal type (ENKL), an Epstein–Barr virus (EBV)-related malignancy. However, little is known about serum sCD27 expression and its association with the clinical characteristics of, and the CD27/CD70 interaction in, ENKL. In the present study, we show that serum sCD27 is significantly elevated in the sera of patients with ENKL. The levels of serum sCD27 provided excellent diagnostic accuracy for discriminating patients with ENKL from healthy subjects, correlated positively with the levels of other diagnostic markers (lactate dehydrogenase, soluble interleukin-2 receptor, and EBV-DNA), and decreased significantly following treatment. Elevated serum sCD27 levels also correlated significantly with advanced clinical stage and tended to correspond with shorter survival, in patients with ENKL. Immunohistochemistry indicated that CD27-positive tumor-infiltrating immune cells exist adjacent to CD70-positive lymphoma cells. In addition, serum sCD27 levels in patients with CD70-positive ENKL were significantly higher than those in patients with CD70-negative ENKL, suggesting that the intra-tumoral CD27/CD70 interaction boosts the release of sCD27 in serum. Furthermore, the EBV-encoded oncoprotein latent membrane protein 1 upregulated CD70 expression in ENKL cells. Our results suggest that sCD27 may serve as a novel diagnostic biomarker and also may serve as a tool for evaluating the applicability of CD27/CD70-targeted therapies by predicting intra-tumoral CD70 expression and CD27/CD70 interaction in ENKL.
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影响因子：
--
作者：
Kitajima S;Lee KL;Fujioka M;Sun W;You J;Chia GS;Wanibuchi H;Tomita S;Araki M;Kato H;Poellinger L
通讯作者：
Poellinger L
影响因子：
6.4
作者：
Ishii, Hideyuki;Takahara, Miki;Klein, Eva
通讯作者：
Klein, Eva
CD27 在人类 B 细胞恶性肿瘤中的表达和释放。
影响因子：
20.3
作者：
M. Van Oers;S. Pals;L. Evers;C. van der Schoot;G. Koopman;J. Bonfrer;RQ Hintzen;A. Von Dem Borne;R. van Lier
通讯作者：
R. van Lier
鼻外NK/T细胞淋巴瘤，鼻类型：遗传，生物学和临床方面，主要关注爱泼斯坦 - 巴尔病毒关系。
影响因子：
4.5
作者：
Takahara M;Kumai T;Kishibe K;Nagato T;Harabuchi Y
通讯作者：
Harabuchi Y
影响因子：
12.7
作者：
Ishii, Hideyuki;Ogino, Takeshi;Harabuchi, Yasuaki
通讯作者：
Harabuchi, Yasuaki