Cancer Cell Biology
CD137 and CD137 ligand constitutively coexpressed on human T and B leukemia cells signal proliferation and survival
Article first published online: 28 OCT 2003
Copyright © 2003 Wiley-Liss, Inc.
International Journal of Cancer
Volume 108, Issue 3, pages 390–398, 20 January 2004
How to Cite
Palma, C., Binaschi, M., Bigioni, M., Maggi, C. A. and Goso, C. (2004), CD137 and CD137 ligand constitutively coexpressed on human T and B leukemia cells signal proliferation and survival. Int. J. Cancer, 108: 390–398. doi: 10.1002/ijc.11574
- Issue published online: 21 NOV 2003
- Article first published online: 28 OCT 2003
- Manuscript Accepted: 1 SEP 2003
- Manuscript Revised: 16 JUL 2003
- Manuscript Received: 2 APR 2003
- CD137/CD137 ligand;
- T and B leukemia cells;
CD137, a member of the tumor necrosis factor receptor family, provides expansion and survival signal to T cells. Its ligand, CD137L, in addition to its ability to costimulate T cells, signals back into antigen presenting cells promoting their activation and differentiation. Recently, CD137 has been proposed as a therapeutic target to improve and sustain anticancer immune response. Several activated T leukemia and B lymphoma cell lines expressed CD137 or CD137L, respectively, and soluble CD137L has been found in sera of leukemia patients. However, the functionality and role of these costimulatory molecules in hematologic malignancies are until now unknown. Interestingly, we observed constitutive CD137 and CD137L coexpression on both human T and B leukemia cell lines. The constitutive CD137 expression on unstimulated T or B leukemia cells presents some differences compared to CD137 expressed on PMA/ionomycin-activated T leukemia cells. Surprisingly, in spite of the low expression level, both tumor CD137 and CD137L molecules signaled in T and B leukemia cells inducing proliferation and prolonging survival. In addition, CD137/CD137L system ligation opposed the anticancer drug cytotoxic effects, reducing the apoptotic DNA fragmentation and stimulating proliferation of doxorubicin-escaped leukemia cells. Although the role of leukemia CD137/CD137L system in vivo is unknown, these data suggest that these costimulatory molecules might confer an advantage to hematologic tumors promoting survival, sustaining cellular growth and contributing to drug resistance. © 2003 Wiley-Liss, Inc.