CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The immune awakening: Transformative strategies against brain tumors.
The immune awakening: Transformative strategies against brain tumors.
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多形性胶质母细胞瘤仍然是死亡率最高的原发性脑肿瘤,由于其能够逃避中枢神经系统独特的免疫屏障,对积极的常规治疗具有高度耐药性。多种机制赋予该肿瘤耐药性,如MHC分子下调、免疫抑制性细胞因子分泌、代谢重编程、Tregs和髓源性抑制细胞的募集,以及血肿瘤屏障和缺氧所强化的异质性。本综述的目的是探讨神经免疫学不断变化的领域,重点关注免疫系统与中枢神经系统(CNS)之间的相互作用、GBM中的免疫抵抗机制以及免疫治疗方法的新进展。在PubMed、Google Scholar、Cochrane和ClinicalTrials.gov上进行了从建库至2025年5月的全面文献检索,以寻找相关研究。近期研究结果表明,CNS是一个高度受调控的环境,具有受控的驻留和浸润免疫细胞群体。GBM通过多种机制利用这些免疫屏障,最终形成免疫抑制性肿瘤微环境。癌症疫苗、免疫检查点抑制剂、过继性细胞疗法和溶瘤病毒显示出前景,但面临BBB穿透有限、免疫抑制和肿瘤异质性等挑战。肠道微生物组的作用和联合策略在克服免疫治疗耐药性方面日益被认为至关重要。尽管如此,持续的研究对于更好地理解并由此克服耐药性、改善GBM患者的临床结局至关重要。
Glioblastoma multiforme remains the primary brain tumor with the highest mortality rate, which is highly resistant to aggressive conventional therapies, owing to its capacity to evade the central nervous system's distinctive immunological barriers. Several mechanisms confer this tumor resistance, such as down-regulation of MHC molecules, secretion of immunosuppressive cytokines, metabolic reprogramming, recruitment of Tregs and myeloid-derived suppressor cells, and heterogeneity reinforced by the blood-tumor barrier and hypoxia. The purpose of this review is to examine the changing field of neuroimmunology, emphasizing the interactions between the immune system and the central nervous system (CNS), immunological resistance mechanisms in GBM, and new developments in immunotherapeutic approaches.
A comprehensive literature search was conducted from inception till May 2025 on PubMed, Google Scholar, Cochrane and Clinicaltrials. gov to find relevant studies. The recent findings show that CNS is a highly regulated environment with controlled populations of resident and infiltrating immune cells. GBM exploits these immune barriers through various mechanisms, ultimately creating an immunosuppressive tumor microenvironment.
Cancer vaccines, immune checkpoint inhibitors, adoptive cell therapies, and oncolytic viruses, show promise but face challenges like limited BBB penetration, immune suppression, and tumor heterogeneity. The role of the gut microbiome and combinatorial strategies are increasingly recognized as vital in overcoming immunotherapy resistance. Nevertheless, continued research is essential to better understand and thereby overcome resistance and improve clinical outcomes in GBM patients.
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