Autophagy Inhibition Sensitizes Radiotherapy Responses in High-grade Mutant IDH1 Glioma [CUT&Run]

RNA-sequencing, single-cell RNA-sequencing, and Chromatin Immunoprecipitation sequencing followed by analysis shows that human and mouse mIDH1 gliomas exhibit downregulated gene ontologies (GOs) related to mitochondrial metabolism and upregulated autophagy-related GOs.

Decreased mitochondrial metabolism is accompanied by decreased glycolysis, rendering autophagy as a source of energy in mIDH1 gliomas. Mutant IDH1 glioma cells exhibit increased expression of autophagy-related proteins and enhanced LC3 I/II conversion, indicating augmented autophagy. Inhibiting autophagy in vivo by administration of synthetic protein nanoparticles encapsulating autophagy related gene 7 silencing RNA sensitized mIDH1 glioma cells to radiation, resulting in tumor regression, long-term survival, and immunological memory.