PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Menthol nanoliposomes enhanced anti-tumor immunotherapy by increasing lymph node homing of dendritic cell vaccines.
Menthol nanoliposomes enhanced anti-tumor immunotherapy by increasing lymph node homing of dendritic cell vaccines.
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薄荷醇是一种环状萜烯醇,在克服血脑屏障和角质层屏障中发挥关键作用。在此,我们创新性地提出了一种薄荷醇纳米脂质体(Men-nanoLips),可显著增加基于树突状细胞(DC)的抗肿瘤疫苗在淋巴结中的蓄积。具体而言,Men-nanoLips通过降低紧密连接蛋白的表达,有效增强了淋巴内皮细胞(EC)屏障的通透性。有趣的是,Men-nanoLips不仅上调了DCs中CCR7的表达,还增加了淋巴ECs中CCL21的分泌。此外,Men-nanoLips促进了DC疫苗的成熟,表现为共刺激分子表达的增加和伪足样蛋白的上调。凭借Men-nanoLips提供的这些互补机制,靶向引流淋巴结的B16全肿瘤细胞裂解物负载DCs的数量显著增加,并显著增强了DC抗肿瘤疫苗的治疗效果。因此,我们得出结论,Men-nanoLips可为增加DC疫苗的淋巴结归巢提供指导。
Menthol, a cyclic terpene alcohol, plays a critical role in overcoming the blood-brain barrier and stratum corneum barrier.
Herein, we innovatively propose a menthol nanoliposome (Men-nanoLips) that can dramatically increase lymph node accumulation of the dendritic cell (DC)-based anti-tumor vaccines. Specifically, Men-nanoLips efficiently enhanced lymphatic endothelial cell (EC) barrier permeability by reducing the expression of tight junction proteins. And interestingly, Men-nanoLips not only up-regulated the expression of CCR7 in DCs but also increased the secretion of CCL21 in lymphatic ECs.
Moreover, Men-nanoLips promoted DC vaccine maturation as evidenced by increasing the expression of costimulatory molecules and up-regulating the pseudopodia-like protein. With those complementary mechanisms provided by Men-nanoLips, the number of the B16 whole-tumor cell lysate-loaded DCs that target the draining LN enhanced remarkably and significantly boosted the treatment efficacy of DC anti-tumor vaccines.
Therefore, we concluded that Men-nanoLips could be instructive for increasing LN homing of DC vaccines.
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