Human T Cell Receptor γδ Cells Recognize Endogenous Mevalonate Metabolites in Tumor Cells

Journal of Experimental Medicine - Tập 197 Số 2 - Trang 163-168 - 2003
Hans-Jürgen Gober1, Magdalena Kistowska1, Lena Ångman1, Paul Jenö2, Lucia Mori1, Gennaro De Libero1
11Experimental Immunology, Department of Research, University Hospital, Basel
22Department of Biochemistry, Biozentrum, University of Basel, CH-4056 Basel, Switzerland

Tóm tắt

T lymphocytes expressing the T cell receptor (TCR)-γδ recognize unknown antigens on tumor cells. Here we identify metabolites of the mevalonate pathway as the tumor ligands that activate TCR-γδ 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-γδ 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 TCR-γδ 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.

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Thông tin
Thông tin xuất bản

Journal of Experimental Medicine

Tập 197 Số 2

163-168

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