Comparison between glioblastoma and brain metastases: How epigenetic remodeling can enhance immunotherapy

Glioblastoma (GBM) is the most common, aggressive and lethal primary tumor of Central Nervous System (CNS). Despite the standard of care and emerging treatment strategies, patient prognosis remains dismal. Over the past decade, immunotherapy has significantly improved outcomes in several tumors, and the clinical success observed in brain metastases (BM) from extracranial tumors has provided insights into CNS tumor immunobiology. However, immunotherapeutic approaches in GBM have so far yielded limited clinical benefit, underscoring the need to better understand the unique features of its tumor microenvironment (TME). This review compares the immunobiology of GBM and BM to elucidate potential mechanisms underlying immunotherapy failure in GBM. In addition, it explores the potential role of epigenetic drugs in reprogramming the GBM TME toward a more inflamed phenotype, thereby potentially enhancing immunogenicity and improving responsiveness to immunotherapy. Such strategies may offer a promising avenue to harness the immune system and inhibit GBM progression.