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:Next-generation antigen-presenting cell immune therapeutics for gliomas.
Next-generation antigen-presenting cell immune therapeutics for gliomas.
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抗原呈递机制和专业抗原呈递细胞(APC)是对抗癌症的有效免疫反应的基础,尤其是在以T细胞为中心的免疫治疗背景下。树突状细胞(DC)作为金标准APC,在启动和维持有效的抗原特异性适应性免疫中发挥着关键作用。近几十年来,来自循环CD14+单核细胞的体外分化DC已成为基于APC的免疫治疗的参考标准。负载肿瘤相关抗原、合成肽或RNA的DC可激活具有抗肿瘤特性的T细胞。这一策略为替代性抗原呈递疫苗策略的发展铺平了道路,例如单核细胞、B细胞和人工APC,这些策略在临床前癌症模型中已显示出有效的治疗结果。对替代性APC平台的探索源于DC疫苗总体临床效果有限,尤其是在胶质瘤等适应症中,胶质瘤是一种原发性脑肿瘤,以对任何免疫干预均具有耐药性而著称。在这篇综述中,我们围绕原发性脑肿瘤,梳理APC免疫治疗的过去、现在和未来。
Antigen presentation machinery and professional antigen-presenting cells (APCs) are fundamental for an efficacious immune response against cancers, especially in the context of T cell-centric immunotherapy. Dendritic cells (DCs), the gold standard APCs, play a crucial role in initiating and maintaining a productive antigen-specific adaptive immunity. In recent decades, ex vivo-differentiated DCs from circulating CD14+ monocytes have become the reference for APC-based immunotherapy. DCs loaded with tumor-associated antigens, synthetic peptides, or RNA activate T cells with antitumor properties.
This strategy has paved the way for the development of alternative antigen-presenting vaccination strategies, such as monocytes, B cells, and artificial APCs, that have shown effective therapeutic outcomes in preclinical cancer models.
The search for alternative APC platforms was initiated by the overall limited clinical impact of DC vaccines, especially in indications such as gliomas, a primary brain tumor known for resistance to any immune intervention. In this Review, we navigate the APC immune therapeutics' past, present, and future in the context of primary brain tumors.
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