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:Glioblastoma Therapy: Rationale for a Mesenchymal Stem Cell-based Vehicle to Carry Recombinant Viruses.
Glioblastoma Therapy: Rationale for a Mesenchymal Stem Cell-based Vehicle to Carry Recombinant Viruses.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
逃避生长抑制是癌症的重要标志之一。包括胶质母细胞瘤(GB)在内的多数人类癌症中,磷酸酶和张力蛋白同源物(PTEN)及p53肿瘤抑制通路均受到破坏,因此这些信号通路是新型癌症治疗的重要切入点。重组病毒能够选择性杀伤癌细胞,并将治疗基因递送至肿瘤。尤其是溶瘤病毒(OV)已成功用于GB动物模型的基因递送,并显示出缓解肿瘤局部免疫抑制的潜力。然而,在临床研究中,相关全身免疫原性、GB细胞转导效率低以及难以充分到达转移性肿瘤等问题,仍是主要瓶颈。间充质干细胞(MSC)具有趋向肿瘤的特性和免疫豁免特征,可能改善OV的靶向递送。将两种策略结合,有望弥补各自的不足。本文总结相关研究,阐述在GB治疗中重新激活p53和PTEN肿瘤抑制通路的依据,并提出利用MSC作为“特洛伊木马”,将携带溶瘤病毒的载荷送至播散的肿瘤病灶。MSC与OV的整合有望成为癌症治疗的新范式。
Evasion of growth suppression is among the prominent hallmarks of cancer. Phosphatase and tensin homolog (PTEN) and p53 tumor-suppressive pathways are compromised in most human cancers, including glioblastoma (GB). Hence, these signaling pathways are an ideal point of focus for novel cancer therapeutics.
Recombinant viruses can selectivity kill cancer cells and carry therapeutic genes to tumors. Specifically, oncolytic viruses (OV) have been successfully employed for gene delivery in GB animal models and showed potential to neutralize immunosuppression at the tumor site.
However, the associated systemic immunogenicity, inefficient transduction of GB cells, and inadequate distribution to metastatic tumors have been the major bottlenecks in clinical studies. Mesenchymal stem cells (MSCs), with tumor-tropic properties and immune privilege, can improve OVs targeting. Remarkably, combining the two approaches can address their individual issues.
Herein, we summarize findings to advocate the reactivation of tumor suppressors p53 and PTEN in GB treatment and use MSCs as a "Trojan horse" to carry oncolytic viral cargo to disseminated tumor beds. The integration of MSCs and OVs can emerge as the new paradigm in cancer treatment.
MEMBER ACCOUNT
登录成功会直接打开下一页。