Human gamma delta T cells and tumor immunotherapy.
Human Vgamma2Vdelta2 T cells recognize nonpeptide antigens derived from pathogenic microbes in a TCR-dependent manner, such as pyrophosphomonoester compounds from mycobacteria and malaria parasite and alkyl amines from Proteus, suggesting that this subset of gamma delta T cells is involved in infectious immunity. The precise recognition mechanism has been delineated using a site-directed mutagenesis strategy based on crystal structure of gamma delta TCR. On the other hand, several lines of evidence indicate that human gamma delta T cells are involved in tumor immunity. Although activated gamma delta T cells exhibit a cytolytic activity against most of tumor cells, only a small fraction of tumor cells, like Burkitt lymphoma cells and multiple myeloid cells, is recognized by human gamma delta T cells in a TCR-dependent manner. This implicates that human gamma delta T cells have two distinct pathways for anti-tumor immunity. One is a natural killer-like pathway and the other is a TCR-dependent pathway. Recently, it was shown that treatment of human tumor cells with nitrogen-containing bisphosphonates, therapeutic drugs for hypercalcemia in malignancy, generated antigenic structure on the surface of tumor cells, which could be recognized by human gamma delta T cells in a TCR-dependent manner. This tumor labeling system may lead to a novel strategy for cancer immunotherapy.
Tanaka
Yoshimasa
Y
Laboratory of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
D000818:Animals; D050071:Bone Density Conservation Agents / Q000276:immunology / Q000627:therapeutic use*; D004164:Diphosphonates / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D009369:Neoplasms / Q000150:complications / Q000276:immunology* / Q000628:therapy*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D016692:Receptors, Antigen, T-Cell, gamma-delta