Epigenetics and Metabolism Reprogramming Interplay into Glioblastoma: Novel Insights on Immunosuppressive Mechanisms

The central nervous system represents a complex environment in which glioblastoma adapts skillfully, unleashing a series of mechanisms suitable for its efficient development and diffusion. In particular, changes in gene expression and mutational events that fall within the domain of epigenetics interact complexly with metabolic reprogramming and stress responses enacted in the tumor microenvironment, which in turn fuel genomic instability by providing substrates for DNA modifications. The aim of this review is to analyze this complex interaction that consolidates several conditions that confer a state of immunosuppression and immunoevasion, making glioblastoma capable of escaping attack and elimination by immune cells and therefore invincible against current therapies. The progressive knowledge of the cellular mechanisms that underlie the resistance of the glioblastoma represents, in fact, the only weapon to unmask its weak points to be exploited to plan successful therapeutic strategies.

Automated summary

The central nervous system is a complex environment where glioblastoma skillfully adapts and unleashes mechanisms for its development and diffusion. Gene expression changes, epigenetic events, metabolic reprogramming, and stress responses in the tumor microenvironment contribute to genomic instability and immunosuppression that make glioblastoma invincible against immune cells and current therapies. Understanding the cellular mechanisms underlying glioblastoma resistance is crucial for planning effective therapeutic strategies.