中文摘要：
巨噬细胞是介导肿瘤细胞发生抗体依赖性细胞吞噬作用（ADCP）的核心细胞。然而，抗体依赖性细胞吞噬作用要发挥理想的抗肿瘤效果，需尽早给药；且随着肿瘤进展，机体易产生治疗抵抗。本研究探究了抗体依赖性细胞吞噬作用的内在调控机制，并提出一种可显著增强该效应的联合治疗策略。研究证实紫杉醇是一种通用佐剂，可在多种肿瘤模型中高效提升各类抗肿瘤抗体介导的抗体依赖性细胞吞噬作用。紫杉醇并非直接杀伤肿瘤细胞，而是将巨噬细胞重编程为吞噬能力显著增强的表型。经紫杉醇处理后的巨噬细胞会下调细胞表面集落刺激因子 1 受体（CSF1R）；在多种恶性肿瘤中，该受体的表达水平与患者生存期呈负相关。抑制巨噬细胞的集落刺激因子 1 受体表达能够促进巨噬细胞对肿瘤细胞的吞噬，说明集落刺激因子 1 受体参与调控巨噬细胞的吞噬功能。综上，本研究提出一种高效治疗策略：利用经典抗肿瘤药物激活巨噬细胞吞噬功能，进而提升临床抗肿瘤抗体的治疗效果。
英文摘要：
Macrophages are essential in eliciting antibody-dependent cellular phagocytosis (ADCP) of cancer cells. However, a satisfactory anticancer efficacy of ADCP is contingent on early antibody administration, and resistance develops along with cancer progression. Here, we investigate the mechanisms underlying ADCP and demonstrate an effective combinatorial strategy to potentiate its efficacy. We identified paclitaxel as a universal adjuvant that efficiently potentiated ADCP by a variety of anticancer antibodies in multiple cancers. Rather than eliciting cytotoxicity on cancer cells, paclitaxel polarized macrophages toward a state with enhanced phagocytic ability. Paclitaxel-treated macrophages down-regulated cell surface CSF1R whose expression was negatively correlated with patient survival in multiple malignancies. The suppression of CSF1R in macrophages enhanced ADCP of cancer cells, suggesting a role of CSF1R in regulating macrophage phagocytic ability. Together, these findings define a potent strategy for using conventional anticancer drugs to stimulate macrophage phagocytosis and promote the therapeutic efficacy of clinical anticancer antibodies.
论文信息：
论文题目：Promoting antibody-dependent cellular phagocytosis for effective macrophage-based cancer immunotherapy
期刊名称：Science Advances
时间期卷：Vol 8, Issue11(2022)
在线时间：2022年3月18日
DOI: 10.1126/sciadv.abl9171
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体先眼眶后静脉注射，然后腹腔注射维持清除肿瘤模型里巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Science Advances：促进抗体依赖性细胞吞噬作用，构建高效巨噬细胞肿瘤免疫治疗方案。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
In vivo macrophage depletion
Clodronate liposomes and control liposomes (PBS) were purchased from Liposoma (The Netherlands). Macrophages were depleted in mice with the following treatment schedule: 200 μl of either clodronate or liposomal control was injected intravenously via the retro-orbital sinus 24 hours before treatment of the mice with intraperitoneal injection with SW480 (2 × 105) and/or cetuximab antibody. Three days after tumor injection, 100 μl of either clodronate or liposomal control was injected (intraperitoneally) to maintain the depletion of macrophages. Bioluminescence images were captured with Lago X (Spectral Instruments Imaging), and signals were analyzed with the Aura Image software. Mice were then sacrificed on day 7, and peritoneal fluid was collected for macrophage analysis by flow cytometry.
氯膦酸二钠脂质体及对照脂质体（磷酸盐缓冲液型）购自荷兰 Liposoma 公司。
采用如下给药方案对小鼠进行巨噬细胞清除处理：给小鼠腹腔接种 SW480 细胞（2×10⁵个）、或联合西妥昔单抗抗体腹腔注射前 24 h，经眶后静脉丛静脉注射 200 μL 氯膦酸二钠脂质体或空白对照脂质体。肿瘤细胞注射 3 天后，腹腔注射 100 μL 氯膦酸二钠脂质体或对照脂质体，持续维持巨噬细胞清除效果。
采用 Lago X 活体成像系统（Spectral Instruments Imaging 公司）采集生物发光图像，使用 Aura Image 软件分析成像信号。第 7 天处死小鼠，收集腹腔灌洗液，通过流式细胞术检测巨噬细胞相关指标。
巨噬细胞清除材料和方法文献截图：促进抗体依赖性细胞吞噬作用，构建高效巨噬细胞肿瘤免疫治疗方案
