Yucebas Kerem, Ko Sooah, Zhou Jinyu, Hamel Elizabeth M, Hackworth Mia G, Diaz Miranda Edgar Andres, Carpenter Haley S, Hunter Mark I, Khan Omair M, Weissman Irving L, Jin Shiying
Department of Obstetrics, Gynecology and Women's Health, School of Medicine, University of Missouri, Columbia, MO 65211, USA.
College of Arts and Sciences, University of Missouri, Columbia, MO 65211, USA.
PNAS Nexus. 2025 May 5;4(5):pgaf143. doi: 10.1093/pnasnexus/pgaf143. eCollection 2025 May.
The interaction between CD47 expressed on cancer cells and signal regulatory protein-α located on macrophages blocks the phagocytosis of tumor cells by macrophages. Our data reveal that human endometrial cancer cells (hECCs) upregulate the CD47 level on their surface and that there is a high density of tumor-associated macrophages within the microenvironment of human endometrial cancer. In vitro functional assay shows that an anti-CD47 monoclonal antibody (mAb) promotes the phagocytosis of hECCs by macrophages. Systemic and in situ treatments with an anti-CD47 mAb effectively reduce tumor burden in vivo in a genetically engineered mouse model of endometrial cancer. Thus, this study provides preclinical evidence that CD47 blockade using an anti-CD47 mAb to augment macrophage phagocytosis is a potential therapeutic strategy for endometrial cancer.
癌细胞上表达的CD47与巨噬细胞上的信号调节蛋白α之间的相互作用会阻断巨噬细胞对肿瘤细胞的吞噬作用。我们的数据显示，人子宫内膜癌细胞（hECCs）会上调其表面的CD47水平，并且在人子宫内膜癌的微环境中存在高密度的肿瘤相关巨噬细胞。体外功能测定表明，抗CD47单克隆抗体（mAb）可促进巨噬细胞对hECCs的吞噬作用。在子宫内膜癌的基因工程小鼠模型中，用抗CD47 mAb进行全身和原位治疗可有效减轻体内肿瘤负担。因此，本研究提供了临床前证据，即使用抗CD47 mAb阻断CD47以增强巨噬细胞吞噬作用是子宫内膜癌的一种潜在治疗策略。
