Human γδ T Cells and Tumor Immunotherapy
Human Vγ2Vδ2 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 <I>Proteus</I>, suggesting that this subset of γδ 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 γδ TCR. On the other hand, several lines of evidence indicate that human γδ T cells are involved in tumor immunity. Although activated γδ 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 γδ T cells in a TCR-dependent manner. This implicates that human γδ 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 γδ T cells in a TCR-dependent manner. This tumor labeling system may lead to a novel strategy for cancer immunotherapy.
- Journal of clinical and experimental hematopathology
Journal of clinical and experimental hematopathology 46(1), 11-23, 2006-03-01
The Japanese Society for Lymphoreticular Tissue Research