中文摘要：
在细胞周期中终末停滞且表现出明显分泌表型的细胞被称为衰老细胞。这些细胞在肿瘤进展中扮演复杂角色；它们可以根据疾病阶段抑制或促进肿瘤生长。我们开发了一种小鼠模型，可监测并选择性消除高表达细胞周期依赖性激酶抑制因子p16和白介素-6的细胞。这些小鼠被称为SuSe（衰老），并与小鼠乳腺肿瘤病毒–多瘤病毒中期T抗原（MMTV-PyMT）乳腺癌模型交叉。对SuSe/PyMT小鼠的功能特征分析证实，在早期和晚期病变中清除衰老细胞（衰老细胞凋亡）分别加速和减缓了肿瘤生长和转移。肿瘤加速被归因于免疫抑制性、促肿瘤巨噬细胞的扩增。识别出C-C基序趋化因子配体2作为其募集和维持所必需的自分泌趋化因子。清除这些巨噬细胞可以逆转衰老细胞清除的效应，使衰老细胞凋亡即使在早期阶段也具有抗肿瘤效果。我们的结果表明，靶向免疫抑制性巨噬细胞可以在减少不良影响的同时保留衰老细胞凋亡的益处。
英文摘要：
Cells terminally arrested in the cell cycle that exhibit a distinct secretory phenotype are referred to as senescent. These cells play a complex role during tumor progression; they can inhibit or promote tumor growth depending on disease stage. We developed a mouse model that allows monitoring and selective elimination of cells expressing high levels of the cyclin-dependent kinase inhibitor p16 and interleukin-6. These mice, termed SuSe (suicidal senescence), were crossed with the mouse mammary tumor virus–polyomavirus middle T antigen (MMTV-PyMT) model of breast cancer. Functional characterization in SuSe/PyMT mice confirmed that depletion of senescent cells (senolysis) in early and late lesions accelerated and decelerated tumor growth and metastasis, respectively. Tumor acceleration was attributed to expansion of immunosuppressive, protumorigenic macrophages. C-C motif chemokine ligand 2 was identified as an autocrine chemokine essential for their recruitment and maintenance. Depletion of these macrophages reversed the effects of senescent cell clearance, rendering senolysis antitumorigenic even at early stages. Our results suggest that targeting immunosuppressive macrophages can preserve the benefits of senolysis while mitigating adverse effects.
论文信息：
论文题目：Immunosuppressive macrophages determine the effect of cellular senescence on tumor progression
期刊名称：Science Advances
时间期卷：Vol 12, Issue 1(2026)
在线时间：2026年1月1日
DOI：10.1126/sciadv.adx2988
产品信息：
货号：C-005
规格：5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes氯膦酸盐脂质体
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体在小鼠乳腺癌模型清除巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Science Advances：免疫抑制性巨噬细胞决定细胞衰老对肿瘤进展的影响。
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：
Macrophages were depleted in PyMT/SuSe mice by twice-weekly injections of clodronate liposomes (5 mg/ml) or phosphate-buffered saline (PBS) as control (#C-005, Liposoma BV) starting at 9 weeks of age.
For selective CCL2 blocking, 4-week-old PyMT/SuSe mice were treated every 3 days with anti-CCL2 antibody (#BE0185, BioXCell,) at a concentration of 2 μg/g of body weight.
材料和方法文献截图：
