CD137 and CD137 ligand constitutively coexpressed on human T and B leukemia cells signal proliferation and survival

• Published in: International journal of cancer 2004-01, Vol.108 (3), p.390-398
• Main Authors: Palma, Carla, Binaschi, Monica, Bigioni, Mario, Maggi, Carlo Alberto, Goso, Cristina
• Format: Article
• Language: English
• Subjects: 4-1BB Ligand; Antigens, CD - metabolism; Antineoplastic agents; Antineoplastic Agents - pharmacology; apoptosis; Apoptosis - drug effects; Biological and medical sciences; CD137/CD137 ligand; Cell Division - drug effects; Cell Survival; doxorubicin; Doxorubicin - pharmacology; Drug Resistance, Neoplasm; Gene Expression Regulation - drug effects; General aspects; Humans; Leukemia, B-Cell - metabolism; Leukemia, B-Cell - pathology; Leukemia, T-Cell - metabolism; Leukemia, T-Cell - pathology; Medical sciences; Pharmacology. Drug treatments; proliferation; Receptors, Nerve Growth Factor - metabolism; Receptors, Tumor Necrosis Factor - metabolism; Signal Transduction - drug effects; survival; T and B leukemia cells; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - metabolism; Tumor Cells, Cultured - pathology; Tumor Necrosis Factor Receptor Superfamily, Member 9; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.11574

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.