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Human T Cell Receptor γδ Cells Recognize Endogenous Mevalonate Metabolites in Tumor Cells
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 o...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193814/ https://www.ncbi.nlm.nih.gov/pubmed/12538656 http://dx.doi.org/10.1084/jem.20021500 |
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author | Gober, Hans-Jürgen Kistowska, Magdalena Angman, Lena Jenö, Paul Mori, Lucia De Libero, Gennaro |
author_facet | Gober, Hans-Jürgen Kistowska, Magdalena Angman, Lena Jenö, Paul Mori, Lucia De Libero, Gennaro |
author_sort | Gober, Hans-Jürgen |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2193814 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21938142008-04-11 Human T Cell Receptor γδ Cells Recognize Endogenous Mevalonate Metabolites in Tumor Cells Gober, Hans-Jürgen Kistowska, Magdalena Angman, Lena Jenö, Paul Mori, Lucia De Libero, Gennaro J Exp Med Article 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. The Rockefeller University Press 2003-01-20 /pmc/articles/PMC2193814/ /pubmed/12538656 http://dx.doi.org/10.1084/jem.20021500 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Gober, Hans-Jürgen Kistowska, Magdalena Angman, Lena Jenö, Paul Mori, Lucia De Libero, Gennaro Human T Cell Receptor γδ Cells Recognize Endogenous Mevalonate Metabolites in Tumor Cells |
title | Human T Cell Receptor γδ Cells Recognize Endogenous Mevalonate Metabolites in Tumor Cells |
title_full | Human T Cell Receptor γδ Cells Recognize Endogenous Mevalonate Metabolites in Tumor Cells |
title_fullStr | Human T Cell Receptor γδ Cells Recognize Endogenous Mevalonate Metabolites in Tumor Cells |
title_full_unstemmed | Human T Cell Receptor γδ Cells Recognize Endogenous Mevalonate Metabolites in Tumor Cells |
title_short | Human T Cell Receptor γδ Cells Recognize Endogenous Mevalonate Metabolites in Tumor Cells |
title_sort | human t cell receptor γδ cells recognize endogenous mevalonate metabolites in tumor cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193814/ https://www.ncbi.nlm.nih.gov/pubmed/12538656 http://dx.doi.org/10.1084/jem.20021500 |
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