摘要：不同于PD-1和CTLA-4介導(dǎo)的特異性免疫檢查點(diǎn)調(diào)控，信號調(diào)節(jié)蛋白a（SIRPa）信號軸被發(fā)現(xiàn)可調(diào)控髓系免疫細(xì)胞介導(dǎo)的非特異性免疫反應(yīng)。CD47-SIRPa信號通路介導(dǎo)的“不要吃我”信號，與鈣網(wǎng)蛋白-低密度脂蛋白受體相關(guān)蛋白信號通路介導(dǎo)的“吃了我”信號相互制約平衡，共同調(diào)控免疫細(xì)胞對腫瘤細(xì)胞的吞噬作用。過去的研究報(bào)道，在惡性血液系統(tǒng)腫瘤（如急性髓系白血?。┖蛯?shí)體瘤等多種腫瘤組織中都有CD47分子的過表達(dá)，提示了阻斷CD47信號通路可能有潛在的抗腫瘤價(jià)值。近年來，抗CD47抗體等靶向此通路的分子在不同的腫瘤治療上有了很大的進(jìn)展。然而，此腫瘤新療法仍存在著一些重要挑戰(zhàn)，比如在CD47介導(dǎo)的抗癌治療臨床轉(zhuǎn)化中，“抗原沉默”等局限性仍需要科研工作者引起高度重視。

關(guān)鍵詞：抗體，CD47，免疫檢查點(diǎn)，吞噬作用，信號調(diào)節(jié)蛋白α，腫瘤

“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