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:Challenges and opportunities for cancer stem cell-targeted immunotherapies include immune checkpoint inhibitor, cancer stem cell-dendritic cell vaccine, chimeric antigen receptor immune cells, and modified exosomes.
Challenges and opportunities for cancer stem cell-targeted immunotherapies include immune checkpoint inhibitor, cancer stem cell-dendritic cell vaccine, chimeric antigen receptor immune cells, and modified exosomes.
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癌症干细胞(CSCs)与肿瘤微环境(TME)相关。CSCs 诱导肿瘤发生、肿瘤复发和进展,以及对标准疗法的耐药。事实上,由于其干性或自我更新特性,CSCs 对当前癌症治疗构成了越来越大的挑战。异质性 CSCs 与周围 TME 组分及肿瘤支持性免疫细胞之间的分子和细胞相互作用,显示出协同效应,导致治疗失败。在免疫抑制性 TME 中,CSCs 表达多种免疫调节蛋白、生长因子、代谢物和细胞因子,并产生外泌体——一种细胞外囊泡——以保护自身免受宿主免疫监视。其中,鉴定和应用 CSC 来源的外泌体可被视为开发消除 CSCs 或癌症的治疗方法的方向,此外还可靶向重塑 TME 组成的调节因子,正如本研究中所综述的那样。
在此,我们介绍 CSCs 的作用,以及它们与 TME 的相互作用如何使免疫治疗复杂化,然后介绍基于 CSC 的免疫治疗及这些疗法的局限性。
我们描述在 TME 中诱导免疫抑制的肿瘤/CSC 来源外泌体的生物学和作用,最后介绍它们在未来开发基于 CSC 的靶向免疫治疗中的潜力。
Cancer stem cells (CSCs) are associated with the tumor microenvironment (TME). CSCs induce tumorigenesis, tumor recurrence and progression, and resistance to standard therapies. Indeed, CSCs pose an increasing challenge to current cancer therapy due to their stemness or self-renewal properties. The molecular and cellular interactions between heterogeneous CSCs and surrounding TME components and tumor-supporting immune cells show synergistic effects toward treatment failure.
In the immunosuppressive TME, CSCs express various immunoregulatory proteins, growth factors, metabolites and cytokines, and also produce exosomes, a type of extracellular vesicles, to protect themselves from host immune surveillance. Among these, the identification and application of CSC-derived exosomes could be considered for the development of therapeutic approaches to eliminate CSCs or cancer, in addition to targeting the modulators that remodel the composition of the TME, as reviewed in this study.
Here, we introduce the role of CSCs and how their interaction with TME complicates immunotherapies, and then present the CSC-based immunotherapy and the limitation of these therapies.
We describe the biology and role of tumor/CSC-derived exosomes that induce immune suppression in the TME, and finally, introduce their potentials for the development of CSC-based targeted immunotherapy in the future.
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