Specific gain-of-function mutations in the enzyme IDH1 (IDH-MUT) frequently occur early in human glioma. In the Journal of Clinical Investigation, Okada and colleagues investigate the functional effects of IDH-MUT using human glioma samples and a novel orthotopic mouse model. The presence of IDH-MUT in human glioma is associated with lower numbers of infiltrating cytotoxic T lymphocytes (CTLs), as well as reduced expression of mRNA encoding effector molecules (e.g., GZMA) and the T cell homing chemokines CXCL9 and CXCL10. Mouse glioma cell lines transfected with IDH-MUT and implanted in recipients show similar reductions in CTL signature. The presence of IDH-MUT reduces glioma production of CXCL9 and CXCL10 at least in part through the loss of the transcription factor STAT1. Specific inhibition of IDH-MUT improved the efficacy of therapeutic peptide vaccination in the orthotopic mouse model of glioma. Targeting of mutant IDH1 activity may therefore be a useful approach in the treatment of glioma.
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Fehervari, Z. Glioma immune evasion. Nat Immunol 18, 487 (2017). https://doi.org/10.1038/ni.3736
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DOI: https://doi.org/10.1038/ni.3736
