中文摘要：
在細胞周期中終末停滯且表現出明顯分泌表型的細胞被稱為衰老細胞。這些細胞在腫瘤進展中扮演復雜角色；它們可以根據疾病階段抑制或促進腫瘤生長。我們開發了一種小鼠模型，可監測并選擇性消除高表達細胞周期依賴性激酶抑制因子p16和白介素-6的細胞。這些小鼠被稱為SuSe（衰老），并與小鼠乳腺腫瘤病毒–多瘤病毒中期T抗原（MMTV-PyMT）乳腺癌模型交叉。對SuSe/PyMT小鼠的功能特征分析證實，在早期和晚期病變中清除衰老細胞（衰老細胞凋亡）分別加速和減緩了腫瘤生長和轉移。腫瘤加速被歸因于免疫抑制性、促腫瘤巨噬細胞的擴增。識別出C-C基序趨化因子配體2作為其募集和維持所必需的自分泌趨化因子。清除這些巨噬細胞可以逆轉衰老細胞清除的效應，使衰老細胞凋亡即使在早期階段也具有抗腫瘤效果。我們的結果表明，靶向免疫抑制性巨噬細胞可以在減少不良影響的同時保留衰老細胞凋亡的益處。
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.
論文信息：
論文題目：Immunosuppressive macrophages determine the effect of cellular senescence on tumor progression
期刊名稱：Science Advances
時間期卷：Vol 12, Issue 1(2026)
在線時間：2026年1月1日
DOI：10.1126/sciadv.adx2988
產品信息：
貨號：C-005
規格：5ml
品牌：Liposoma
產地：荷蘭
名稱：Clodronate Liposomes氯膦酸鹽脂質體
辦事處：靶點科技
Clodronate Liposomes氯膦酸鹽脂質體在小鼠乳腺癌模型清除巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Science Advances：免疫抑制性巨噬細胞決定細胞衰老對腫瘤進展的影響。
Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除巨噬細胞的材料和方法：
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.
材料和方法文獻截圖：
