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.

中文翻译：

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吞噬检查点作为癌症免疫治疗的新靶点。

针对适应性免疫检查点的癌症免疫疗法显着改善了多种转移性和难治性癌症类型的患者预后。然而，新兴研究表明，先天免疫检查点通过吞噬作用干扰恶性细胞的检测和清除并抑制先天免疫感应，在肿瘤介导的免疫逃逸中也发挥着关键作用，因此可能成为癌症的潜在靶点免疫疗法。事实上，临床前研究和早期临床数据已经确定了靶向吞噬检查点的前景，例如 CD47 信号调节蛋白 α (SIRPα) 轴，无论是单独使用还是与其他癌症疗法联合使用。在这篇综述中，我们重点介绍了目前对癌细胞如何通过破坏吞噬清除来逃避免疫系统的理解，以及吞噬检查点阻断对诱导抗肿瘤免疫反应的影响。鉴于先天免疫细胞在引发适应性免疫反应中的作用，更好地了解抑制基本免疫监视过程（例如吞噬作用和先天免疫感应）的肿瘤内在过程，可以为开发高效的联合免疫治疗策略铺平道路调节先天性和适应性抗肿瘤免疫反应。