Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Amankulor, NM; Kim, Y; Arora, S; Kargl, J; Szulzewsky, F; Hanke, M; Margineantu, DH; Rao, A; Bolouri, H; Delrow, J; Hockenbery, D; Houghton, AM; Holland, EC.
Mutant IDH1 regulates the tumor-associated immune system in gliomas.
Genes Dev. 2017; 31(8):774-786
Doi: 10.1101/gad.294991.116
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- Co-authors Med Uni Graz
- Kargl Julia
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- Abstract:
- Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 (wtIDH1/2) tumors. Although there are many factors underlying the differences in survival between these two tumor types, immune-related differences in cell content are potentially important contributors. In order to investigate the role of IDH mutations in immune response, we created a syngeneic pair mouse model for mutant IDH1 (muIDH1) and wtIDH1 gliomas and demonstrated that muIDH1 mice showed many molecular and clinical similarities to muIDH1 human gliomas, including a 100-fold higher concentration of 2-hydroxygluratate (2-HG), longer survival time, and higher CpG methylation compared with wtIDH1. Also, we showed that IDH1 mutations caused down-regulation of leukocyte chemotaxis, resulting in repression of the tumor-associated immune system. Given that significant infiltration of immune cells such as macrophages, microglia, monocytes, and neutrophils is linked to poor prognosis in many cancer types, these reduced immune infiltrates in muIDH1 glioma tumors may contribute in part to the differences in aggressiveness of the two glioma types. © 2017 Amankulor et al.; Published by Cold Spring Harbor Laboratory Press.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Brain Neoplasms - enzymology
- Brain Neoplasms - genetics
- Brain Neoplasms - immunology
- Chemotaxis - genetics
- DNA Methylation -
- Disease Models, Animal -
- Glioma - enzymology
- Glioma - genetics
- Glioma - immunology
- Humans -
- Immune System - physiopathology
- Isocitrate Dehydrogenase - genetics
- Isocitrate Dehydrogenase - metabolism
- Leukocyte Common Antigens - metabolism
- Leukocytes - pathology
- Mice -
- Mutation -
- Neutrophil Infiltration - genetics
- Neutrophils - pathology
- Find related publications in this database (Keywords)
- IDH mutation
- immuno-oncology
- glioma