Inflammatory response and cell cycle pathways contribute to innate resistance to Anti-PD-1 therapy in glioblastoma

Abstract

Glioblastoma (GBM), as the most prevalent malignant primary brain tumor in adults, is characterized by limited treatment options and poor prognosis. Immune checkpoint inhibitors have revolutionized cancer therapy, prompting interest in their potential application in GBM treatment. This study identified potential targets for enhancing the efficacy of GBM immunotherapy by a statistical analysis of genomic and transcriptional data coupled with an exploration of the molecular mechanisms governing patient responses to immunotherapy. Our analysis revealed that the effectiveness of anti-PD-1 immunotherapy in GBM is closely associated with the mutational burden of the tumor and the age at which treatment is initiated. In addition, we found that the gene set signature of cell cycle regulation is upregulated, while the immune response regulation pathways are enriched in the tumors from non-responsive patients. These findings underscore the potential effectiveness of targeting these pathways in the context of anti-PD-1 immunotherapy, with the promise of enhancing patient outcomes in GBM.