Interplay between ATRX and IDH1 mutations governs innate immune responses in diffuse gliomas.

ABSTRACT: Stimulating the innate immune system has been explored as a therapeutic option for the treatment of gliomas. Inactivating mutations in ATRX, defining molecular alterations in IDH-mutant astrocytomas, have been implicated in dysfunctional immune signaling. However, little is known about the interplay between ATRX loss and IDH mutation on innate immunity. To explore this, we generated ATRX-deficient glioma models in the presence and absence of the IDH1^R132H mutation. ATRX-deficient glioma cells are sensitive to dsRNA-based innate immune agonism and exhibit impaired lethality and increased T-cell infiltration in vivo. However, the presence of IDH1^R132H dampens baseline expression of key innate immune genes and cytokines in a manner restored by genetic and pharmacological

SUBMITTER: Hariharan S 

PROVIDER: S-EPMC10810843 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature