肿瘤细胞治疗研究
英文原题：Sialylated CD43 forms a glyco-immune barrier that restrains antileukemic immunity.
巨噬细胞通过吞噬作用发挥抗肿瘤活性，但增强吞噬作用的疗法并未改善急性髓系白血病（AML）的结局。
巨噬细胞通过吞噬作用发挥抗肿瘤活性，但增强吞噬作用的治疗策略并未改善急性髓系白血病（AML）的预后。为鉴定吞噬作用调控因子，我们在与人巨噬细胞共培养的人 AML 细胞中进行了 CRISPR 敲除筛选。我们发现，“别吃我”信号 CD47 抑制小鼠巨噬细胞吞噬作用，但不抑制人巨噬细胞吞噬作用。然而，O-连接糖基化和唾液酸化是吞噬作用的强负调控因素。在 AML 中，细胞表面黏蛋白样糖蛋白 CD43 是这些通路的主要效应分子。CD43 对吞噬作用的抑制依赖于其胞外域的长度，而不依赖于巨噬细胞唾液酸受体 SIGLEC-1、SIGLEC-7 和 SIGLEC-9。CD43 的抑制作用不仅限于人巨噬细胞，还扩展至NK 细胞和 T 细胞。因此，CD43 形成了一道糖免疫屏障，同时限制固有免疫和适应性抗白血病免疫。
Macrophages exert antitumorigenic activity through phagocytosis, but phagocytosis-enhancing therapeutics have not improved acute myeloid leukemia (AML) outcomes. To identify phagocytosis regulators, we performed CRISPR knockout screens in human AML cells cocultured with human macrophages. We found that the "don't eat me" signal CD47 inhibited mouse but not human macrophage phagocytosis. However, O-linked glycosylation and sialylation were strong negative regulators of phagocytosis. In AML, the cell surface mucin-like glycoprotein CD43 was the major effector of these pathways. Inhibition of phagocytosis by CD43 was dependent on the length of its ectodomain and independent of the macrophage sialic acid receptors SIGLEC-1, SIGLEC-7, and SIGLEC-9. The inhibitory effects of CD43 extended beyond human macrophages to natural killer and T cells. Thus, CD43 forms a glyco-immune barrier that restrains both innate and adaptive antileukemic immunity.
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