CD200R1-CD200 免疫检查点以不同于 SIRPα-CD47 的方式抑制吞噬作用，从而抑制肿瘤生长

中文摘要：

靶向巨噬细胞抑制受体，如信号调节蛋白α (SIRPα)，在癌症治疗中是一条有前景的途径。尽管SIRPα的配体CD47在肿瘤细胞上广泛表达，但其在所有正常细胞上的同时存在引发了对毒性和疗效的担忧。本研究确定CD200R1，它与特定类型肿瘤和有限正常细胞上的CD200结合，作为吞噬作用的替代抑制检查点。阻断或去除巨噬细胞中的CD200R1或肿瘤细胞中的CD200，可以增加吞噬作用并抑制肿瘤生长。在人类中，CD200R1主要在免疫抑制性巨噬细胞中表达，并由白细胞介素-4诱导。与利用酪氨酸磷酸酶Src同源2域磷酸酶(SHP)-1和SHP-2的SIRPα不同，CD200R1通过激酶Csk介导其抑制作用。结合CD200R1-CD200和SIRPα-CD47的阻断，进一步增强了吞噬作用，并减少CD200表达肿瘤的生长，相比于单独的阻断。因此，靶向CD200R1-CD200是巨噬细胞中免疫检查点阻断的有前景策略，可以单独进行，也可以与其他检查点的阻断结合。

英文摘要：

Targeting macrophage inhibitory receptors like signal regulatory protein α (SIRPα) is a promising avenue in cancer treatment. Whereas the ligand of SIRPα, CD47, is widely expressed on tumor cells, its simultaneous presence on all normal cells raises concerns about toxicity and efficacy. This study identifies CD200R1, which binds CD200 on specific tumor types and limited normal cells, as an alternative inhibitory checkpoint for phagocytosis. Blocking or removing CD200R1 from macrophages or CD200 from tumor cells increases phagocytosis and suppresses tumor growth. In humans, CD200R1 is mainly expressed in immunosuppressive macrophages and is induced by interleukin-4. Unlike SIRPα that utilizes phosphatases Src homology 2 domain phosphatase (SHP)−1 and SHP-2, CD200R1 mediates its inhibitory effect via the kinase Csk. Combined CD200R1-CD200 and SIRPα-CD47 blockade further boosts phagocytosis and reduces tumor growth of CD200-expressing tumors, compared to either blockade alone. Thus, targeting CD200R1-CD200 is a promising strategy for immune checkpoint blockade in macrophages, either alone or alongside blockade of other checkpoints.

论文信息：

论文题目：D200R1-CD200 checkpoint inhibits phagocytosis differently from SIRPα-CD47 to suppress tumor growth

期刊名称：Nature Communications

时间期卷：16, Article number: 5145 (2025)

在线时间：2025年6月3日

DOI：doi.org/10.1038/s41467-025-60456-3

产品信息：

货号：CP-005-005

规格：5ml+5ml

品牌：Liposoma

产地：荷兰

名称：Clodronate Liposomes and Control Liposomes

办事处：Target Technology（靶点科技）

注射方式：静脉注射

剂量和频率：100ul/次，建模前1次，隔3天，一共注射4次。肿瘤模型。

氯膦酸盐二钠脂质体清除单核巨噬细胞，在肿瘤模型中单核巨噬细胞功能研究，荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：CD200R1-CD200 免疫检查点以不同于 SIRPα-CD47 的方式抑制吞噬作用，从而抑制肿瘤生长

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：

In vivo mouse tumor models

Tumor injections and treatments: For WEHI-231 and A20, pools of three clones of Tac+ GFP+ cells (1 × 106 each) were injected intravenously (WEHI-231) or subcutaneously (A20) in 6-10-week-old Rag1−/− mice. Alternatively, for WEHI-231, a polyclonal population of luciferase+ Tac+ GFP+ WEHI-231 cells (1 × 106) was used. At the indicated times after tumor cell injection, mice received intraperitoneal injections every 2 days of Tac mAb 7G7 or Ctrl mAb (200 µg), along with either CD200 mAb OX-90 (200 µg), SIRPα mAb 27 (200 μg), both mAbs, or Ctrl mAb 2A3 (200 µg). For macrophages depletion in vivo, mice were injected I.V. with 100 μl of clodronate liposomes or control liposomes (Liposoma BV, Amsterdam, Netherlands) every 4 days, starting from 1 day prior to tumor transplantation and until the end of the experiment.