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:CCR7 Mediated Mimetic Dendritic Cell Vaccine Homing in Lymph Node for Head and Neck Squamous Cell Carcinoma Therapy.
免疫疗法已被公认为头颈部鳞状细胞癌(HNSCC)最有前景的治疗策略之一。
免疫治疗已被公认为头颈部鳞状细胞癌(HNSCC)最有前景的治疗策略之一。作为免疫治疗的先驱趋势,树突状细胞(DC)疫苗已显示出启动免疫应答的能力,但免疫原性不足和淋巴结(LN)靶向效率低,导致其在临床试验中的治疗效果缺乏充分证据。在此,我们通过融合肿瘤来源外泌体(TEX)和树突状细胞膜囊泡(DCMV),开发了一种杂合纳米疫苗(Hy-M-Exo)。该杂合纳米疫苗从DCMV继承了淋巴归巢的关键蛋白CCR7,并表现出增强的LN靶向效率。同时,杂合纳米疫苗中保留的肿瘤抗原和内源性危险信号激活抗原提呈细胞(APC),引发了强效的T细胞应答。此外,纳米疫苗Hy-M-Exo在HNSCC小鼠模型中显示出良好的治疗效果。这些结果表明,Hy-M-Exo具有较高的临床价值,可作为抗肿瘤免疫治疗的一种可行策略。
Immunotherapy has been recognized as one of the most promising treatment strategies for head and neck squamous cell carcinoma (HNSCC). As a pioneering trend of immunotherapy, dendritic cell (DC) vaccines have displayed the ability to prime an immune response, while the insufficient immunogenicity and low lymph node (LN) targeting efficiency, resulted in an unsubstantiated therapeutic efficacy in clinical trials. Herein, a hybrid nanovaccine (Hy-M-Exo) is developed via fusing tumor-derived exosome (TEX) and dendritic cell membrane vesicle (DCMV). The hybrid nanovaccine inherited the key protein for lymphatic homing, CCR7, from DCMV and demonstrated an enhanced efficiency of LN targeting. Meanwhile, the reserved tumor antigens and endogenous danger signals in the hybrid nanovaccine activated antigen presenting cells (APCs) elicited a robust T-cell response. Moreover, the nanovaccine Hy-M-Exo displayed good therapeutic efficacy in a mouse model of HNSCC. These results indicated that Hy-M-Exo is of high clinical value to serve as a feasible strategy for antitumor immunotherapy.
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