Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand.
Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Anticancer Res. 2024 Nov;44(11):4929-4940. doi: 10.21873/anticanres.17318.
BACKGROUND/AIM: Macrophage-mediated cancer immune evasion is modulated by the balance between "the cluster of differentiation 47 (CD47), an anti-phagocytic signal" and "calreticulin (CALR), a pro-phagocytic signal". CD47 is highly expressed in various types of cancer. However, the expression profiles of CD47 and CALR in breast cancer, especially in different hormone receptor subtypes, and the effects of CD47 blockade in macrophage-mediated therapy are not well understood.
The expression levels of CD47 and CALR were investigated in breast cancer and adjacent normal tissues using immunohistochemistry. To study the effects of CD47 blockade therapy, CD47 and CALR expression in breast cancer cell lines were determined. In vitro macrophage-mediated phagocytosis of breast cancer upon treatment with a monoclonal CD47 antibody (B6H12) were performed.
CD47 and CALR were overexpressed in breast cancer tissues and their up-regulation was associated with hormone receptor subtypes. Patients with Luminal A breast cancer had higher levels of CD47, while patients with triple-negative breast cancer (TNBC) had higher levels of CALR. The levels of CD47 and CALR were also elevated in breast cancer cell lines of Luminal A (MCF-7) and TNBC (MDA-MB-231) subtypes. Interestingly, the expression ratio of surface CD47/CALR was significantly higher in MCF-7. Moreover, in vitro phagocytosis assays revealed that blockage of CD47 enhanced macrophage-mediated activity in both cancer cells with dramatically higher degrees of phagocytosis in MCF-7.
The expression profiles of CD47 and CALR in breast cancer subtypes and the benefit of CD47 blocking-based immunotherapy are herein provided.
背景/目的：巨噬细胞介导的癌症免疫逃逸受“分化簇 47（CD47），一种抗吞噬信号”和“钙网蛋白（CALR），一种促吞噬信号”之间的平衡调节。CD47 在各种类型的癌症中高度表达。然而，CD47 和 CALR 在乳腺癌中的表达谱，特别是在不同激素受体亚型中的表达谱，以及 CD47 阻断在巨噬细胞介导的治疗中的作用尚不清楚。
使用免疫组织化学法检测乳腺癌及相邻正常组织中 CD47 和 CALR 的表达水平。为了研究 CD47 阻断治疗的效果，测定了乳腺癌细胞系中 CD47 和 CALR 的表达。用单克隆 CD47 抗体（B6H12）处理后，进行体外巨噬细胞介导的乳腺癌吞噬作用。
CD47 和 CALR 在乳腺癌组织中过度表达，其上调与激素受体亚型有关。Luminal A 型乳腺癌患者的 CD47 水平较高，而三阴性乳腺癌（TNBC）患者的 CALR 水平较高。Luminal A（MCF-7）和 TNBC（MDA-MB-231）亚型的乳腺癌细胞系中 CD47 和 CALR 的水平也升高。有趣的是，MCF-7 中表面 CD47/CALR 的表达比值明显更高。此外，体外吞噬试验显示，CD47 阻断增强了两种癌细胞中巨噬细胞介导的活性，MCF-7 中的吞噬作用程度明显更高。
本文提供了乳腺癌亚型中 CD47 和 CALR 的表达谱以及基于 CD47 阻断的免疫治疗的益处。
