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.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Exploring the Potential of Receptor Silencing in the Tumor Microenvironment by RNA Interference.
较常采用的传统治疗方法存在副作用和耐药性问题。
癌症是一种由遗传和表观遗传因素引起的异质性疾病,导致信号通路和调控过程发生改变。总体而言,较常用的传统治疗存在副作用和耐药性。由于肿瘤微环境中细胞组成多样,通过 RNA 干扰(RNAi)抑制细胞通讯已成为调控与癌变相关受体表达的一种策略。本综述探讨了 RNAi 介导的受体沉默作为一种修饰肿瘤微环境的策略,主要作用于肿瘤细胞,增强其对免疫细胞破坏的易感性,并降低对传统治疗的耐药性。在肿瘤微环境中,沉默 PD-1 和 CTLA-4 等免疫检查点已显示出恢复 T 细胞功能和增强过继细胞疗法疗效的能力。此外,靶向 G 蛋白偶联受体,包括 CXCR4、CCR5 和 A2aR,以及生长因子受体如 VEGFR 和 EGFR,还有白细胞介素受体,可干扰对肿瘤促进至关重要的通路,从而减少血管生成、转移和免疫抑制。这些策略利用先进的递送系统,包括纳米颗粒和外泌体,并表明沉默多个靶点可比单靶点方法产生更有效的抗肿瘤效果,凸显了 RNA 干扰在癌症治疗中的巨大潜力。
Cancer is a heterogeneous disease caused by genetic and epigenetic factors, leading to alterations in signaling pathways and regulatory processes. Overall, the more commonly employed conventional treatments present side effects and resistance. Due to the diverse cellular composition of the tumor microenvironment, inhibition of cell communication by RNA interference (RNAi) has emerged as a strategy to regulate the expression of receptors linked to carcinogenesis. This review examines RNAi-mediated receptor silencing as a strategy to modify the tumor microenvironment, primarily in tumor cells, enhancing its vulnerability to immune cell destruction and reducing resistance to conventional therapies. In the tumor microenvironment, the silencing of immune checkpoints like PD-1 and CTLA-4 has demonstrated the ability to restore T cell function and enhance the efficacy of adoptive cell therapies. Additionally, the targeting of G protein-coupled receptors, including CXCR4, CCR5, and A2aR, as well as growth factor receptors such as VEGFR and EGFR, and interleukin receptors, interferes with pathways that are critical for tumor promotion, resulting in diminished angiogenesis, metastasis, and immunosuppression. These strategies utilize advanced delivery systems, including nanoparticles and exosomes, and show that silencing multiple targets can produce more effective antitumor outcomes than single-target methods, underscoring the significant potential of RNA interference in cancer treatment.
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