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摘要：不同于PD-1和CTLA-4介导的特异性免疫检查点调控，信号调节蛋白a（SIRPa）信号轴被发现可调控髓系免疫细胞介导的非特异性免疫反应。CD47-SIRPa信号通路介导的“不要吃我”信号，与钙网蛋白-低密度脂蛋白受体相关蛋白信号通路介导的“吃了我”信号相互制约平衡，共同调控免疫细胞对肿瘤细胞的吞噬作用。过去的研究报道，在恶性血液系统肿瘤（如急性髓系白血病）和实体瘤等多种肿瘤组织中都有CD47分子的过表达，提示了阻断CD47信号通路可能有潜在的抗肿瘤价值。近年来，抗CD47抗体等靶向此通路的分子在不同的肿瘤治疗上有了很大的进展。然而，此肿瘤新疗法仍存在着一些重要挑战，比如在CD47介导的抗癌治疗临床转化中，“抗原沉默”等局限性仍需要科研工作者引起高度重视。 关键词：抗体，CD47，免疫检查点，吞噬作用，信号调节蛋白α，肿瘤 引用本文 Xiang YR, Liu L. “Eating” Cancer cells by blocking CD47 signaling: Cancer therapy by targeting the innate immune checkpoint. Cancer Transl Med 2017;3(6):200-208. “Eating” Cancer cells by blocking CD47 signaling: Cancer therapy by targeting the innate immune checkpoint Yi-Rong Xiang, Li Liu Abstract: Differing from the adaptive immune checkpoint mediated by programmed cell death-1 (PD-1) PD-1-ligand or CTLA-4, the CD47 and signal regulatory protein α (SIRPα) axis is emerging as a novel innate immune checkpoint of the immune cells of myeloid lineage. A balance should be established between the dual signals, the “Don't eat me signal” of CD47-SIRPα and the “Eat me signal” of calreticulin/low-density lipoprotein receptor-related protein. The enhanced expression of CD47 molecule has been found in many cancer tissues, including malignant blood tumors (acute myeloid leukemia) and solid tumors. A therapeutic value could be achieved by counteracting the expression of CD47 in cancer cells. In the recent years, great progress has been made to develop anticancer therapies by targeting CD47 (e.g., anti-CD47 antibody), in various types of cancer. However, there are a few challenges, like “antigen sink” in the clinical translation of CD47-mediated anticancer therapies, the attention to which is crucial. Key words: Antibody, CD47, immune checkpoint, phagocytosis, signal-regulatory protein a, tumor |
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