Antitumor Activity and Some Immunological Properties of γδ T-Cells from Patients with Gastrointestinal Carcinomas

Abstract

Objectives: Human γδ T-cells expressing Vγ2Jγ1.2Vδ2-TCR recognize microbial pyrophosphomonoesters in an MHC-independent manner and exert cytotoxic activity on a wide variety of tumor cells. In the present study, the immunological properties of γδ T-cells derived from patients with gastrointestinal carcinomas were examined and compared with those from healthy adult individuals, aiming to develop a novel cancer immunotherapy using γδ T-cells stimulated with one of the nonpeptide antigens, 2-methyl-3-butenyl-1-pyrophosphate (2M3B1PP). Materials and Methods: Peripheral blood mononuclear cells (PBMs) and tumor-associated lymphocytes (TAL) were obtained from patients with gastrointestinal carcinomas. The mononuclear cells were stimulated with 2M3B1PP for 2 weeks and the expanded γδ T cells were examined for cytokine production upon T-cell receptor (TCR) engagement and cytotoxic activity against allogeneic tumors and autologous tumor cells. For comparison, PBMCs derived from healthy adult volunteers were similarly stimulated with 2M3B1PP and the resulting γδ T-cells were analyzed for effector functions. Results: All the peripheral blood- and tumor-associated γδ T-cell preparations from patients with gastrointestinal carcinomas proliferated vigorously in response to 2M3B1PP to comparable levels to those from healthy donors. When challenged with CD3 monoclonal antibodies, the carcinoma patient-derived γδ T-cells secreted a large amount of inflammatory cytokine, IFN-γ, and exhibited a potent cytotoxic activity against allogeneic tumor cell lines as well as autologous tumor cells. Conclusion: Both peripheral blood- and tumor-associated γδ T-cells derived from patients with gastrointestinal carcinomas were as immunologically active as those from healthy individuals and could be utilized for a novel cancer immunotherapy for gastrointestinal malignancies.