肿瘤细胞治疗研究
英文原题：Metabolic and Post-Translational Vulnerabilities of Glioblastoma: Disulfidptosis, Glycosylation, and Implications for CAR-T Therapy.
Metabolic and Post-Translational Vulnerabilities of Glioblastoma: Disulfidptosis, Glycosylation, and Implications for CAR-T Therapy.
胶质母细胞瘤（GB）仍是治疗抵抗性最强的实体瘤之一，其特征是显著的代谢可塑性、瘤内异质性和高度免疫抑制的微环境。
胶质母细胞瘤（GB）仍是最耐受治疗的实体瘤之一，具有显著代谢可塑性、肿瘤内异质性及高度免疫抑制性微环境。CAR-T（CAR-T）细胞等免疫疗法虽在血液系统恶性肿瘤中显示出前景，但治疗GB的疗效有限。新兴证据表明，肿瘤特异性代谢依赖及翻译后修饰（PTM）可能构成可利用的脆弱性。本综述讨论近期描述的一种受调控细胞死亡方式——二硫死亡；在还原能力有限时，二硫键应激可驱动该过程，其可能是GB中具有情境依赖性的代谢-氧化还原脆弱性。我们进一步讨论胶质母细胞瘤中蛋白质糖基化变化及糖萼结构如何调节细胞存活、死亡信号和免疫识别。特别关注CAR-T靶向的表面抗原，包括EGFR/EGFRvIII、IL-13Rα2、间皮素、B7-H3、HER2和GD2的糖基化，以及糖链依赖的表位可及性如何限制疗效。最后，我们区分二硫死亡——其与CAR-T应答的直接相关性尚待确立——与糖基化及糖萼重塑；后两者是影响靶抗原可及性和免疫识别的更直接决定因素。针对这些脆弱性的治疗策略，可能为改善GB的CAR-T及联合治疗提供合理机会。
Glioblastoma (GB) remains one of the most therapy-resistant solid tumors, characterized by profound metabolic plasticity, intratumoral heterogeneity, and a highly immunosuppressive microenvironment. While immunotherapies such as chimeric antigen receptor T (CAR-T) cells have shown promise in hematological malignancies, their efficacy in GB has been limited. Emerging evidence suggests that tumor-specific metabolic dependencies and post-translational modifications (PTMs) may represent exploitable vulnerabilities. This review discusses disulfidptosis, a recently described form of regulated cell death driven by disulfide stress under conditions of limited reducing capacity, as a context-dependent metabolic-redox vulnerability in GB. We further discuss how altered protein glycosylation and glycocalyx architecture in glioblastoma regulate cell survival, death signaling, and immune recognition. Particular emphasis is placed on the glycosylation of surface antigens targeted by CAR-T cells, including EGFR/EGFRvIII, IL-13R 2, mesothelin, B7-H3, HER2, and GD2, and on how glycan-dependent epitope accessibility may limit therapeutic efficacy. Finally, we distinguish disulfidptosis, whose direct relevance to CAR-T-cell responses remains to be established, from glycosylation and glycocalyx remodeling as more direct determinants of target-antigen accessibility and immune recognition. Therapeutic strategies addressing these vulnerabilities may provide rational opportunities to improve CAR-T-based and combinatorial therapies for GB.
MEMBER ACCOUNT
登录成功会直接打开下一页。
