Mevalonate Metabolism in Immuno-Oncology

Frontiers in Immunology

Georg Gruenbacher¹  Martin Thurnher¹ 

[1] Immunotherapy Unit, Department of Urology, Medical University of Innsbruck, Innsbruck, Austria;

关键词: mevalonate;    metabolism;    transcellular;    cholesterol;    fatty acid oxidation;    immune cells;   

DOI  :  10.3389/fimmu.2017.01714

来源: DOAJ

【 摘 要 】

Immuno-oncology not only refers to the multifaceted relationship between our immune system and a developing cancer but also includes therapeutic approaches that harness the body’s immune system to fight cancer. The recognition that metabolic reprogramming governs immunity was a key finding with important implications for immuno-oncology. In this review, we want to explore how activation and differentiation-induced metabolic reprogramming affects the mevalonate pathway for cholesterol biosynthesis in immune and cancer cells. Glycolysis-fueled mevalonate metabolism is a critical pathway in immune effector cells, which may, however, be shared by cancer stem cells, complicating the development of therapeutic strategies. Additional engagement of fatty acidy oxidation, as it occurs in regulatory immune cells as well as in certain tumor types, may influence mevalonate pathway activity. Transcellular mevalonate metabolism may play an as yet unanticipated role in the crosstalk between the various cell types and may add another level of complexity. In humans, a subset of γδ T cells is specifically adapted to perform surveillance of mevalonate pathway dysregulation. While the mevalonate pathway remains an important target in immuno-oncology, in terms of personalized medicine, it may be the type or stage of a malignant disease that determines whether mevalonate metabolism requires training or attenuation.

【 授权许可】

Unknown