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

By Hans-Jürgen Gober, M. Kistowska, L. Angman, P. Jenö, L. Mori, G. De Libero. Journal of Experimental Medicine, 2003

833 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5335a67eef7ca43dcc448b2916cdb3937b7ab08e