Immune Cell may Explain Breast, Prostate Cancer Vaccine Resistance

Tumour-infiltrating gamma delta T-cells found at high levels in breast and prostate cancer suppress the cancer-fighting potential of the immune system and may explain the ineffectiveness of vaccines in those diseases, said Baylor College of Medicine researchers in a report that appears in the journal Immunity. (These cells are part of the innate or non-specific immune system.)

"Many epithelial cell-derived cancers such as those of the prostate and breast may contain high percentages of the gamma delta T-cells," said Dr. Rong-Fu Wang, professor in the BCM Center for Cell and Gene Therapy. "Those gamma delta T-cells can potently mediate immune suppression and that causes the problem."By contrast, he said, few of these T-cells are found in melanoma, a cancer that is receptive to treatment with cancer vaccines or immunotherapy."I think that the higher percentage of the gamma delta T-cells may be responsible for the poor immunogenicity of breast and prostate cancer and could probably explain why they do not respond well to immunotherapy," he said.The next question, he said, is how to overcome the suppressive effect these cells have on the immune system. One strategy would be to use ligands (small strands of genetic material) that bind to human Toll-like receptor 8 to reverse the suppressive function of tumour-infiltrating gamma delta T-cells.Wang and his colleagues used such ligands to reverse the suppressive effects of CD4+ regulatory T cells, another group of T-cells that mediate important immune regulation in a previous study. They found that the same ligand reverses the suppressive effect of tumour-infiltrating gamma delta T-cells as well."We showed that the suppressive function of these gamma delta T-cells can be reversed by the same mechanism controlled by human Toll-like receptor 8 signalling pathway," he said.Because he has identified a new type of immune cells that suppresses the ability of the immune system to fight breast and prostate cancer, Wang knows he has uncovered a new feature of how host immune cells interact with tumour cells. He said a better understanding of the interplay between immune cells and tumour cells will be the key to devising new strategies for cancer immunotherapy.Using the same ligand or strand of genetic material could reverse the suppressive effects of both kinds of regulatory T-cells on the cancer-fighting immune system and may be a new avenue of treatment to pursue in the future, he said.Others who took part in the research include: Drs. Guangyong Peng, Helen Y. Wang, Weiyi Peng, Yukiko Kiniwa and Kook Heon Seo, all of BCM.Funding for this work came from the American Cancer Society, the Cancer Research Institute and the National Institutes of Health.(Source: Immunity : Kimberlee Barbour : Baylor College of Medicine : September 2007)