Expression of CD137 on hodgkin and reed-sternberg cells inhibits T-cell activation by eliminating CD137 ligand expression

Weng Tong Ho, Wan Lu Pang, Siew Meng Chong, Antonio Castella, Suhail Al-Salam, Teng Ee Tan, Mei Chung Moh, Liang Kai Koh, Shu Uin Gan, Cheong Kin Cheng, Herbert Schwarz

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

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-g 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.

Original languageEnglish
Pages (from-to)652-661
Number of pages10
JournalCancer Research
Volume73
Issue number2
DOIs
Publication statusPublished - Jan 15 2013
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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