IDH Mutation-derived Immunosuppression

Mutations in isocitrate dehydrogenase (IDH)1 and IDH2 are early and frequent (70-80%) genetic alterations in lower-grade glioma (LGG) as well as in secondary glioblastoma that progresses from LGG. We recently reported for the first time that IDH mutations in glioma cells lead to decreased STAT1 levels, which down-regulate T-cell-attracting chemokines, such as CXCL10, and inhibit CD8+ T-cell accumulation in gliomas. Pharmacological inhibition of mutant IDH reversed suppression of STAT1, CXCL10, and CD8+ T-cell accumulation in gliomas and improved the efficacy of immunotherapy with vaccines, demonstrating a novel immunosuppression mechanism in IDH mutant gliomas.

Related Publication

Kohanbash G, Carrera DA, Shrivastav S, Ahn BJ, Jahan N, Mazor T, Chheda ZS, Downey KM, Watchmaker PB, Beppler C, Warta R, Amankulor NA, Herold-Mende C, Costello JF and Okada H. IDH mutations suppress STAT1 and CD8+ T-cell accumulation in gliomas. J. Clin Invest 127 (4) 1425-1437 (2017). PMC5373859 

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