Inhibitory immune checkpoint blockade has been one of the most significant advances in anticancer therapy of the past decade. Research so far has largely focused on improving adaptive immune functions, but recent studies have indicated that the signal-regulatory protein (SIRP)α–CD47 pathway, a phagocytosis checkpoint in macrophages and other innate immune cells, may be an interesting therapeutic target. Here, we summarize current knowledge about SIRPα–CD47 blockade, and highlight key issues for future investigations. These include the targeting of prophagocytic receptors (Fc receptors or otherwise) to complement SIRPα–CD47 blockade, the understanding of constraints on phagocytosis other than the SIRPα–CD47 checkpoint and the contribution of immune cells other than macrophages. A better understanding of how SIRPα–CD47 blockade works may aid in identifying patients suitable for this therapy, avoiding potential toxicities and designing optimal combination therapies.

中文翻译：

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SIRPα-CD47免疫检查点阻断剂在抗癌治疗中的作用

在过去的十年中，抑制性免疫检查站封锁一直是抗癌治疗领域最重要的进展之一。到目前为止，研究主要集中在改善适应性免疫功能上，但是最近的研究表明，信号调节蛋白（SIRP）α-CD47途径（巨噬细胞和其他先天免疫细胞的吞噬检查点）可能是一个有趣的治疗靶点。在这里，我们总结了有关SIRPα-CD47阻滞剂的最新知识，并重点介绍了未来研究的关键问题。这些包括靶向吞噬细胞受体（Fc受体或其他受体）以补充SIRPα-CD47阻断作用，对除SIRPα-CD47检查点以外的吞噬作用限制的理解以及除巨噬细胞以外的免疫细胞的作用。