摘要
肿瘤细胞和与肿瘤相关的基质细胞(例如免疫细胞,内皮细胞和间充质细胞)产生了肿瘤微环境(TME),可在促进肿瘤细胞生长,生长和扩散的同时抑制抗肿瘤免疫反应。有效的抗肿瘤干预措施必须考虑到TME的复杂性,并利用免疫疗法和化学疗法相结合的方法。因此,肿瘤治疗的目的是直接击中肿瘤细胞并逆转内皮和免疫细胞的过敏。已经证明使用与TNFα相关的肽或抗体片段与化学治疗剂结合的肿瘤血管系统的选择性靶向对内皮细胞以及对先天性和适应性免疫反应具有有效的刺激作用。这些减少了所用单一药剂剂量的药物组合已使相关的副作用减至最小。在这篇综述中,我们将分析人类和肿瘤小鼠模型中不同的TNFα介导的靶向肿瘤血管的疗法,重点是自然杀伤细胞与树突状细胞之间的相互作用以及TNFα触发肿瘤血管活化和正常化的能力。也将讨论使用抗血管生成免疫调节药物改善基于TNFα的疗法,这种药物可能将TME从免疫抑制转变为免疫刺激。
关键词: 肿瘤血管,TNFα,靶向免疫疗法,化学疗法,L19,NK细胞,树突状细胞,T细胞反应。
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