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Published on: September 1, 2018
Antitumor activity and some immunological properties of gammadelta T-cells from patients with gastrointestinal
Minoru Murayama1, Yoshimasa Tanaka, Junji Yagi
1Department of Surgery, Tokyo Women's Medical University Medical Center East, Arakawa-Ku, Tokyo 116-8567, Japan.
Objectives:
Human gammadelta T-cells expressing Vgamma2Jgamma1.2Vdelta2-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 gammadelta 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 gammadelta 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 gammadelta 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 gammadelta T-cells were analyzed for effector functions.
Results:
All the peripheral blood- and tumor-associated gammadelta 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 gammadelta T-cells secreted a large amount of inflammatory cytokine, IFN-gamma, and exhibited a potent cytotoxic activity against allogeneic tumor cell lines as well as autologous tumor cells.
Conclusion:
Both peripheral blood- and tumor-associated gammadelta 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.
Insights
Gammadelta T-cells from gastrointestinal cancer patients show potent anti-tumor activity, similar to healthy individuals. These cells, stimulated with 2-methyl-3-butenyl-1-pyrophosphate (2M3B1PP), offer a promising avenue for novel cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Cellular Therapy
Background:
- Human gammadelta T-cells recognize microbial antigens independently of MHC.
- These cells possess cytotoxic activity against various tumor cells.
- Gastrointestinal carcinomas present a significant challenge for current cancer treatments.
Purpose of the Study:
- To investigate the immunological properties of gammadelta T-cells from gastrointestinal cancer patients.
- To compare these properties with gammadelta T-cells from healthy individuals.
- To explore the potential of 2-methyl-3-butenyl-1-pyrophosphate (2M3B1PP) for cancer immunotherapy.
Main Methods:
- Peripheral blood mononuclear cells (PBMs) and tumor-associated lymphocytes (TAL) were isolated from gastrointestinal carcinoma patients.
- Cells were stimulated with 2M3B1PP for two weeks.
- Expanded gammadelta T-cells were analyzed for cytokine production and cytotoxic activity against allogeneic and autologous tumors. PBMCs from healthy donors served as controls.
Main Results:
- Gammadelta T-cells from both patients and healthy donors proliferated robustly in response to 2M3B1PP.
- Carcinoma patient-derived gammadelta T-cells secreted significant amounts of IFN-gamma upon TCR engagement.
- These cells demonstrated potent cytotoxic activity against both allogeneic tumor cell lines and autologous tumor cells.
Conclusions:
- Gammadelta T-cells from gastrointestinal cancer patients exhibit comparable immunological activity to those from healthy individuals.
- Both peripheral blood and tumor-associated gammadelta T-cells are viable candidates for cancer immunotherapy.
- Stimulation with 2M3B1PP holds promise for developing novel immunotherapies for gastrointestinal malignancies.
