Glioblastoma: Relationship between Metabolism and Immunosuppressive Microenvironment

Abstract

Glioblastoma (GBM) is the most aggressive brain tumor in adults and is characterized by an immunosuppressive microenvironment. Different factors shaping this tumor microenvironment (TME) regulate tumor initiation, progression, and treatment response. Genetic alterations and metabolism pathways are two main elements that influence tumor immune cells and TME. In this manuscript, we review how both factors can contribute to an immunosuppressive state and overview the strategies being tested.

Kynureninase Promotes Immunosuppression and Predicts Survival in Glioma Patients: In Silico Data Analyses of the Chinese Glioma Genome Atlas (CGGA) and of the Cancer Genome Atlas (TCGA)

“…The GBM tumor microenvironment is highly heterogeneous and consists of different cell types involved in promoting immune evasion [ 10 ]. Moreover, a close relationship between metabolic reprogramming and immunosuppressive TME has been observed [ 11 ], with immune evasion being the main hallmark described in GBM [ 6 ]. Thus, alterations in metabolic pathways can promote an immunosuppressive TME through the release of different oncometabolites [ 12 ].…”

Glioblastoma imitating a cavernoma radiologically: A unique image report

“…[15] Therefore, to holistically appreciate glioblastoma progression, morphological and genetic alterations have been combined with traditional pathological descriptions of the disease to produce a dichotomous classification. [3] At the core of this classification lies the Isocitrate dehydrogenase IDH-1 mutation status; thus, glioblastoma can now be categorized as either wild-type or mutant, which are near-perfect analogs to the previous WHO classification of primary and secondary glioblastoma, respectively. [9] IDH-1 wild-type glioblastomas are the most frequent (90%) and are predominant in patients over 60 years of age, whereas IDH-1 mutant is less frequent (10%) and arise in younger patients with a history of lower-grade glioma.…”

Chaperone-Mediated Autophagy in Pericytes: A Key Target for the Development of New Treatments against Glioblastoma Progression

“…Traits present in the tumor microenvironment (TME) or peritumoral niche have been considered very useful to understand the biology of GB progression as they contribute to tumor immune evasion and support tumor growth [ 8 , 11 ]. GB cells are capable of expressing and secreting immunosuppressive factors (e.g., TGF-β, IL-1, and IL-10), which suppress anti-tumor mechanisms of the surrounding immune cells [ 8 , 12 , 13 ]. Different immune populations of microglia and macrophages, known as tumor-associated macrophages (TAMs), are regularly found in the peritumoral niche [ 11 , 12 ].…”

“…Two types of TAMs have been characterized: M1, which are pro-inflammatory/anti-tumoral; M2, which are anti-inflammatory/pro-tumoral [ 14 ]. GB cell phenotypes are driven by the tumor microenvironment, with M2 TAMs being associated with tumor progression [ 13 ]. Even B-lymphocytes overexpressing tumor-beneficial immune-inhibitory molecules have been found infiltrating the tumor microenvironment [ 15 ].…”