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Roles of Idiotype-Specific T Cells in Myeloma Cell Growth and Survival: Th1 and CTL Cells Are Tumoricidal while Th2 Cells Promote Tumor Growth

Department of Lymphoma and Myeloma, Division of Cancer Medicine, and Center for Cancer Immunology Research, University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Qing Yi, Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0903, Houston, TX 77030. Phone: 713-563-9065; Fax: 713-563-9241; E-mail: qyi{at}mdanderson.org.

Key Words: Multiple myeloma • idiotype • T-cell subsets • immunotherapy • murine model

Idiotype (Id) protein, secreted by myeloma cells, is a tumor-specific antigen. Id-based immunotherapy has been explored in patients with myeloma, and results were disappointing. Although previous studies have shown that Id-specific CTLs are able to lyse myeloma cells, it is unclear whether other types of Id-specific T cells, such as type-1 T-helper (Th1) and type-2 T-helper (Th2) cells, are also able to suppress or kill myeloma cells. Using a 5T murine myeloma model, we generated T-cell clones of different subsets and examined their function in the context of myeloma cells. Id-specific CTLs specifically lysed myeloma cells via MHC class I, perforin, and Fas ligand (FasL), and Th1, but not Th2, cells lysed the myeloma cells by FasL–Fas interaction. CTL and Th1 cells also suppressed the growth and function of myeloma cells, whereas Th2 cells promoted the proliferation and enhanced the secretion of Id protein and cytokines by myeloma cells. CTL and Th1, but not Th2, cells were able to eradicate established myeloma in vivo after adoptive transfer. These results show that Id-specific CTL and Th1 are promising effector cells, whereas Th2 provide no protection and may even promote tumor progression in vivo. [Cancer Res 2008;68(20):8456–64]