Expression of CD137 on Hodgkin and Reed-Sternberg Cells Inhibits T-cell Activation by Eliminating CD137 Ligand Expression
Expression of CD137 on Hodgkin and Reed-Sternberg Cells Inhibits T-cell Activation by Eliminating CD137 Ligand Expression
复制标题
DOI：
10.1158/0008-5472.can-12-3849
复制
发表时间：
2013-01-15
期刊：
影响因子：
11.2
通讯作者：
Schwarz, Herbert
中科院分区：
文献类型：
--
作者：
Ho, Weng Tong;Pang, Wan Lu;Schwarz, Herbert
霍奇金淋巴瘤是由少数恶性霍奇金细胞和里德-斯滕伯格 (HRS) 细胞引起的，这些细胞会招募大量炎症细胞。 HRS细胞在绝大多数免疫细胞中的长期存活表明它们已经发展出有效的免疫逃逸机制。我们报道，TNF 受体家族成员 CD137 (TNFRSF9) 在 HRS 细胞上表达，而 HRS 细胞最常源自的正常 B 细胞不表达 CD137。在 53 例经典霍奇金淋巴瘤病例中，有 48 例在 HRS 细胞上检测到 CD137。异位表达的 CD137 通过胞吞作用从 HRS 细胞转移到邻近的 HRS 和抗原呈递细胞，组成性表达 CD137 配体（CD137L 和 TNFSF9），与 CD137L 相关联，并且 CD137-CD137L 复合物被内化。 CD137L 从 HRS 和抗原呈递细胞表面消失，导致 T 细胞通过 CD137 的共刺激减少，从而减少 IFN-γ 释放和增殖。我们的结果揭示了 CD137L 表达的新调节机制，可介导 HRS 细胞的免疫逃逸，并且他们将 CD137 确定为霍奇金淋巴瘤免疫治疗的候选靶点。癌症研究； 73(2)； 652-61。 (C)2012 AACR。
Hodgkin lymphoma is caused by a minority population of malignant Hodgkin and Reed-Sternberg (HRS) cells that recruit an abundance of inflammatory cells. The long-term survival of HRS cells among the vast majority of immune cells indicates that they have developed potent immune escape mechanisms. We report that the TNF receptor family member CD137 (TNFRSF9) is expressed on HRS cells, while normal B cells, from which HRS cells are most often derived, do not express CD137. In 48 of 53 cases of classical Hodgkin lymphoma, CD137 was detected on HRS cells. Ectopically expressed CD137 transferred by trogocytosis from HRS cells to neighboring HRS and antigen-presenting cells, which constitutively express the CD137 ligand (CD137L and TNFSF9), became associated with CD137L and the CD137-CD137L complex was internalized. Disappearance of CD137L from the surface of HRS and antigen-presenting cells led to reduced costimulation of T cells through CD137, reducing IFN-gamma release and proliferation. Our results reveal a new regulatory mechanism for CD137L expression that mediates immune escape by HRS cells, and they identify CD137 as a candidate target for immunotherapy of Hodgkin lymphoma. Cancer Res; 73(2); 652-61. (C)2012 AACR.