Antitumor activity and some immunological properties of gammadelta T-cells from patients with gastrointestinal carcinomas.
OBJECTIVE
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).


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.


CONCLUSIONS
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.
Murayama
Minoru
M
Department of Surgery, Tokyo Women's Medical University Medical Center East, Arakawa-Ku, Tokyo 116-8567, Japan.
Tanaka
Yoshimasa
Y
Yagi
Junji
J
Uchiyama
Takehiko
T
Ogawa
Kenji
K
D000469:Alkaline Phosphatase / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000941:Antigens / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D009943:Organophosphorus Compounds / Q000276:immunology / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
C533571:2-methyl-3-butenyl-1-pyrophosphate; D000911:Antibodies, Monoclonal; D000941:Antigens; D017252:CD3 Complex; D016207:Cytokines; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000469:Alkaline Phosphatase