Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON, Canada; Department of Pathology, University of Hong Kong, Hong Kong, Hong Kong.
Curr Opin Biotechnol. 2021 Apr;68:181-185. doi: 10.1016/j.copbio.2020.11.013. Epub 2020 Dec 24.
Mutations in the genes encoding isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) are key drivers of diverse cancers, including gliomas and hematological malignancies. IDH mutations cause neomorphic enzymatic activity that results in the production of the oncometabolite 2-hydroxyglutarate (2-HG). In addition to 2-HG's well-known effects on tumor cells themselves, it has become increasingly clear that 2-HG directly influences the tumor microenvironment (TME). In particular, the non-cell-autonomous impact of 2-HG on the immune system likely plays a major role in shaping disease development and response to therapy. It is therefore critical to understand how IDH mutations affect the metabolism, epigenetics, and functions of tumor-infiltrating immune cells. Such knowledge may point towards new therapeutic approaches to treat IDH-mutant cancers.
IDH1 和 IDH2 基因突变是多种癌症（包括神经胶质瘤和血液恶性肿瘤）的关键驱动因素。IDH 突变导致新的酶促活性，导致致癌代谢物 2-羟戊二酸（2-HG）的产生。除了 2-HG 对肿瘤细胞本身的众所周知的影响外，越来越明显的是，2-HG 直接影响肿瘤微环境（TME）。特别是，2-HG 对免疫系统的非细胞自主影响可能在塑造疾病发展和对治疗的反应方面发挥主要作用。因此，了解 IDH 突变如何影响肿瘤浸润免疫细胞的代谢、表观遗传学和功能至关重要。这种知识可能指向治疗 IDH 突变型癌症的新治疗方法。
