Molecular characteristics and modifications of glioblastoma affecting the efficacy of immunotherapy

Glioblastoma is a highly aggressive brain tumor characterized by complex genetic, molecular, and epigenetic features that present significant challenges for treatment. This review explores recent advances in understanding the molecular and epigenetic landscape of glioblastoma, with particular emphasis on epigenetic modifications such as DNA methylation, histone changes, and N6-methyladenosine regulation, including representative regulators such as AlkB homolog 5 and methyltransferase-like 14 that link tumor plasticity to immune evasion and therapeutic response. Accumulating evidence suggests that these modifications are associated with the regulation of gene expression, tumor progression, and immune evasion, and may influence the tumor's response to immunotherapy. The review further discusses the interplay between genetic mutations, such as those in Epidermal Growth Factor Receptor and Phosphatase and Tensin Homolog, and immune responses within the tumor microenvironment, which is characterized by immunosuppressive cell populations like regulatory T cells and myeloid-derived suppressor cells. By integrating molecular profiling, epigenetic analysis, and immunotherapy, researchers aim to develop personalized therapeutic strategies to enhance glioblastoma treatment outcomes. Additionally, the review highlights the potential of combining immunotherapy with targeted therapies and radiotherapy to overcome tumor resistance mechanisms. The use of advanced technologies, including single-cell sequencing and machine learning, is identified as crucial in uncovering the complexities of tumor-immune interactions, leading to more refined and effective treatment strategies. Ultimately, a comprehensive approach integrating genetic and epigenetic factors offers promising prospects for transforming glioblastoma into a more manageable condition, improving patient prognosis and quality of life.