Torrisi Filippo, D'Aprile Simona, Denaro Simona, Pavone Anna Maria, Alberghina Cristiana, Zappalà Agata, Giuffrida Rosario, Salvatorelli Lucia, Broggi Giuseppe, Magro Gaetano Giuseppe, Calabrese Vittorio, Vicario Nunzio, Parenti Rosalba
Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, 95123 Catania, Italy.
Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", Anatomic Pathology, University of Catania, 95123 Catania, Italy.
Antioxidants (Basel). 2023 Jan 18;12(2):220. doi: 10.3390/antiox12020220.
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.
中枢神经系统是一个复杂的环境，胶质母细胞瘤能巧妙地适应其中，释放出一系列适合其高效发展和扩散的机制。特别是，属于表观遗传学领域的基因表达变化和突变事件与肿瘤微环境中发生的代谢重编程和应激反应复杂地相互作用，而肿瘤微环境又通过为DNA修饰提供底物来加剧基因组不稳定。本综述的目的是分析这种复杂的相互作用，这种相互作用巩固了几种导致免疫抑制和免疫逃逸状态的条件，使胶质母细胞瘤能够逃避免疫细胞的攻击和清除，因此对当前的治疗方法具有抗性。事实上，对胶质母细胞瘤耐药性背后细胞机制的逐步了解是揭示其弱点以制定成功治疗策略的唯一武器。
