文章：

吞噬检查点作为肿瘤免疫治疗的新靶点

Phagocytosis checkpoints as new targets for cancer immunotherapy

原文发布日期：2019-08-28

DOI: 10.1038/s41568-019-0183-z

类型: Review Article

开放获取: 否

英文摘要：

Cancer immunotherapies targeting adaptive immune checkpoints have substantially improved patient outcomes across multiple metastatic and treatment-refractory cancer types. However, emerging studies have demonstrated that innate immune checkpoints, which interfere with the detection and clearance of malignant cells through phagocytosis and suppress innate immune sensing, also have a key role in tumour-mediated immune escape and might, therefore, be potential targets for cancer immunotherapy. Indeed, preclinical studies and early clinical data have established the promise of targeting phagocytosis checkpoints, such as the CD47–signal-regulatory protein α (SIRPα) axis, either alone or in combination with other cancer therapies. In this Review, we highlight the current understanding of how cancer cells evade the immune system by disrupting phagocytic clearance and the effect of phagocytosis checkpoint blockade on induction of antitumour immune responses. Given the role of innate immune cells in priming adaptive immune responses, an improved understanding of the tumour-intrinsic processes that inhibit essential immune surveillance processes, such as phagocytosis and innate immune sensing, could pave the way for the development of highly effective combination immunotherapy strategies that modulate both innate and adaptive antitumour immune responses.

摘要翻译： 

靶向适应性免疫检查点的癌症免疫疗法已显著改善多种转移性及难治性癌症类型的患者预后。然而，最新研究表明，先天性免疫检查点通过干扰吞噬作用对恶性细胞的识别清除并抑制先天性免疫感应，在肿瘤介导的免疫逃逸中同样发挥关键作用，因此可能成为癌症免疫治疗的潜在靶点。临床前研究及早期临床数据已证实，靶向吞噬检查点（如CD47-信号调节蛋白α轴）单独或联合其他癌症疗法的应用前景。本文重点阐述当前对癌细胞通过破坏吞噬清除作用实现免疫逃逸的机制认知，以及吞噬检查点阻断对诱导抗肿瘤免疫应答的影响。鉴于先天性免疫细胞在启动适应性免疫应答中的作用，深入理解肿瘤内在进程如何抑制吞噬作用与先天性免疫感应等关键免疫监视机制，将为开发同时调控先天性与适应性抗肿瘤免疫应答的高效联合免疫治疗策略奠定基础。

原文链接：

Phagocytosis checkpoints as new targets for cancer immunotherapy