期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 197, 期 2, 页码 163-168出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20021500
关键词
antigen recognition; tumor antigen; HMGR; IPP; bisphosphonate drugs
T lymphocytes expressing the T cell receptor (TCR)-gammadelta recognize unknown antigens on tumor cells. Here we identify metabolites of the mevalonate pathway as the tumor ligands that activate TCR-gammadelta cells. In tumor cells, blockade of hydroxy-methylglutaryl-CoA reductase (HMGR), the rate limiting enzyme of the mevalonate pathway, prevents both accumulation of mevalonate metabolites and recognition by TCR-gammadelta cells. When metabolite accumulation is induced by overexpressing HMGR, or by treatment with nitrogen-containing bisphosphonate drugs, tumor cells derived from many tissues acquire the capacity to stimulate the same TCP-gammadelta population. Accumulation of mevalonate metabolites in tumor cells is a powerful danger signal that activates the immune response and may represent a novel target of tumor immunotherapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据