Glioblastoma (GBM) is a highly aggressive primary brain cancer with dismal prognoses despite current standards of care. Immunotherapy is being explored for GBM, given its promising results in other solid malignancies; however, the results from early clinical studies in GBM are disappointing. It has been discovered that GBM has numerous mechanisms of immune resistance, including the physical blood–brain barrier, high intratumoral and intertumoral heterogeneity, and numerous cellular and molecular components in the tumor microenvironment (TME) that promote immunosuppression. Furthermore, GBM utilizes numerous metabolic pathways to establish a survival advantage in the TME. Recently, it has begun to become evident that these complex metabolic pathways that promote GBM growth and invasion also contribute to tumor immune resistance. Aerobic glycolysis provides tumor cells with ample ATP while depleting key glucose and increasing acidity in the TME. Increased glutamine, tryptophan, and arginine metabolism deprives T cells of these necessary amino acids for proper anti-tumor function. Sphingolipid metabolism promotes an immunosuppressive phenotype in the TME and affects immune cell trafficking. This review will discuss, in detail, the key metabolic pathways relevant to GBM pathophysiology which also modulate host immunosuppression.
胶质母细胞瘤（GBM）是一种高度侵袭性的原发性脑癌，尽管目前已有标准治疗方案，但其预后仍然极差。鉴于免疫疗法在其他实体瘤中展现出良好前景，研究人员正探索将其应用于GBM治疗，然而早期临床研究结果令人失望。研究发现，GBM具有多重免疫抵抗机制，包括物理性的血脑屏障、高度的瘤内与瘤间异质性，以及肿瘤微环境（TME）中众多促进免疫抑制的细胞与分子成分。此外，GBM通过多种代谢途径在TME中建立生存优势。近期研究逐渐揭示，这些促进GBM生长与侵袭的复杂代谢途径同样参与了肿瘤免疫抵抗过程：有氧糖酵解在为肿瘤细胞提供充足ATP的同时，消耗了关键葡萄糖并增加TME酸度；增强的谷氨酰胺、色氨酸及精氨酸代谢剥夺了T细胞发挥正常抗肿瘤功能所需的必需氨基酸；鞘脂代谢则促进TME免疫抑制表型形成并影响免疫细胞运输。本综述将详细探讨与GBM病理生理相关且能调控宿主免疫抑制的关键代谢途径。
肿瘤(癌症)患者之家