The adaptive immune checkpoints such as PD-1(programmed death-1)/PD-L1 (programmed death-ligand 1) play an important role in cancer immunotherapy, whereas increasing evidence suggests that cancer cell evades immune surveillance by innate immune checkpoints such as SIRPα (signal-regulatory protein α)/CD47 (cluster of differentiation 47). In multiple types of cancer cells and solid tumor tissues, highly expressed CD47 protein level has been observed, which is triggered by some transcription factors including NFκB, Myc, and HIF. As a transmembrane protein, the binding of CD47 to SIRPα ligand on phagocytes results in phagocytosis resistance and cancer cell immune escape. In contrast, CD47-SIRPα interaction blockade enhances cancer cell clearance by phagocytes such as macrophages and dendritic cells (DCs) to activate an innate immune response, whereas this process could promote antigen cross-presentation by antigen present cells (APCs) leading to T cell priming, consequently, activates an adaptive antitumor immune response. In this review, we discussed the current SIRPα-CD47 axis-mediated cancer cell immune escape and immunotherapy, which could provide an effective antitumor strategy by the innate and adaptive immune response.

中文翻译：

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CD47/SIRPα通路介导癌症免疫逃逸和免疫治疗

PD-1（programmed death-1）/PD-L1（programmed death-ligand 1）等适应性免疫检查点在癌症免疫治疗中发挥着重要作用，而越来越多的证据表明癌细胞通过先天免疫检查点逃避免疫监视，例如SIRPα（信号调节蛋白 α）/CD47（分化簇 47）。在多种类型的癌细胞和实体瘤组织中，已观察到高表达的 CD47 蛋白水平，这是由包括 NFκB、Myc 和 HIF 在内的一些转录因子触发的。作为一种跨膜蛋白，CD47 与吞噬细胞上的 SIRPα 配体结合导致吞噬抗性和癌细胞免疫逃逸。相比之下，CD47-SIRPα 相互作用阻断增强了巨噬细胞和树突状细胞 (DC) 等吞噬细胞对癌细胞的清除，从而激活了先天免疫反应，而这一过程可以促进抗原呈递细胞 (APC) 的抗原交叉呈递，从而导致 T 细胞启动，从而激活适应性抗肿瘤免疫反应。在这篇综述中，我们讨论了目前 SIRPα-CD47 轴介导的癌细胞免疫逃逸和免疫治疗，它可以通过先天性和适应性免疫反应提供有效的抗肿瘤策略。