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.
肿瘤细胞治疗研究
英文原题:Exo-nanomaterials in cancer immunotherapy: reprogramming the tumor immune microenvironment.
Exo-nanomaterials in cancer immunotherapy: reprogramming the tumor immune microenvironment.
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免疫疗法如检查点阻断、过继细胞转移和疫苗可诱导持久缓解,但大多数实体瘤仍难治,因为肿瘤免疫微环境(TIME)既具有免疫抑制作用,又难以物理接近。与此同时,细胞外囊泡(EVs)和合成纳米材料已成为互补的免疫信使和可编程载体。外泌体-纳米材料是将EV膜与合成核心融合的杂合体,旨在将EV的生物相容性和转运特性与工程纳米材料的负载能力、模块化和刺激响应性统一起来。在此,我们总结外泌体如何通过分布检查点配体、重编程髓系细胞和调节抗原呈递来塑造TIME,以及如何工程化纳米材料以改善先天激动剂和疫苗货物的肿瘤局部递送。随后,我们概述主要构建路线(包覆、负载和仿生制造)以及能够实现冷肿瘤向热肿瘤转化、检查点阻断增敏和新抗原及核酸疫苗递送的设计模块。最后,我们讨论关键的转化挑战,包括标准化、机制解析、可扩展制造和安全性,并提出免疫设计原则,以指导可重复、基于机制的开发,从而实现实体瘤的持久免疫治疗。
Immunotherapies such as checkpoint blockade, adoptive cell transfer and vaccines can induce durable responses, yet most solid tumors remain refractory because the tumor immune microenvironment (TIME) is both immunosuppressive and physically difficult to access.
In parallel, extracellular vesicles (EVs) and synthetic nanomaterials have emerged as complementary immune messengers and programmable carriers. Exo-nanomaterials, hybrids that fuse EV membranes with synthetic cores, aim to unite EV biocompatibility and trafficking with the loading capacity, modularity and stimulus-responsiveness of engineered nanomaterials.
Here, we summarize how exosomes shape the TIME by distributing checkpoint ligands, reprogramming myeloid cells and modulating antigen presentation, and how nanomaterials are engineered to improve tumor-localized delivery of innate agonists and vaccine cargos.
We then outline major construction routes (coating, loading and mimetic fabrication) and design modules that enable cold-to-hot conversion, sensitization to checkpoint blockade, and delivery of neoantigen and nucleic-acid vaccines.
Finally, we discuss key translational challenges, including standardization, mechanism deconvolution, scalable manufacturing and safety, and propose immune-by-design principles to guide reproducible, mechanism-grounded development toward durable immunotherapy in solid tumors.
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