Is CD47 an innate immune checkpoint for tumor evasion?
Is CD47 an innate immune checkpoint for tumor evasion?
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DOI：
10.1186/s13045-016-0381-z
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发表时间：
2017-01-11
影响因子：
28.5
通讯作者：
Fu YX
中科院分区：
文献类型：
--
作者：
Liu X;Kwon H;Li Z;Fu YX
分化簇47（CD 47）（也称为整合素相关蛋白）是免疫球蛋白超家族的普遍表达的糖蛋白，其在自我识别中起关键作用。各种实体和血液癌症利用CD 47表达以逃避免疫学根除，并且其过表达在临床上与较差的复发相关。CD 47介导的免疫逃避背后的一个重要机制是它可以与骨髓细胞上表达的信号调节蛋白-α（SIRPα）相互作用，导致SIRPα细胞质免疫受体酪氨酸基序的磷酸化和含有Src同源2结构域的酪氨酸磷酸酶的募集，最终导致递送抗吞噬细胞-“不要吃我”-信号。鉴于其作为先天免疫和随后的适应性免疫的阴性检查点的重要作用，CD 47-SIRPα轴已被探索为癌症免疫治疗的新靶点，并且其破坏已显示出巨大的治疗前景。事实上，已经发现CD 47阻断抗体在各种临床前模型中降低原发性肿瘤大小和/或转移。在这篇综述中，我们强调了CD 47的各种功能，讨论了先天性和适应性免疫系统产生的抗肿瘤反应，作为管理的抗CD 47阻断抗体的结果，最后阐述了CD 47阻断的临床潜力。我们认为，CD 47是先天免疫和适应性免疫的肿瘤逃避的检查点分子，因此是癌症免疫治疗的一个有前途的靶点。
Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. Various solid and hematologic cancers exploit CD47 expression in order to evade immunological eradication, and its overexpression is clinically correlated with poor prognoses. One essential mechanism behind CD47-mediated immune evasion is that it can interact with signal regulatory protein-alpha (SIRPα) expressed on myeloid cells, causing phosphorylation of the SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and recruitment of Src homology 2 domain-containing tyrosine phosphatases to ultimately result in delivering an anti-phagocytic—“don’t eat me”—signal. Given its essential role as a negative checkpoint for innate immunity and subsequent adaptive immunity, CD47-SIRPα axis has been explored as a new target for cancer immunotherapy and its disruption has demonstrated great therapeutic promise. Indeed, CD47 blocking antibodies have been found to decrease primary tumor size and/or metastasis in various pre-clinical models. In this review, we highlight the various functions of CD47, discuss anti-tumor responses generated by both the innate and adaptive immune systems as a consequence of administering anti-CD47 blocking antibody, and finally elaborate on the clinical potential of CD47 blockade. We argue that CD47 is a checkpoint molecule for both innate and adaptive immunity for tumor evasion and is thus a promising target for cancer immunotherapy.