免疫抑制性巨噬細(xì)胞決定細(xì)胞衰老對(duì)腫瘤進(jìn)展的影響

中文摘要：

在細(xì)胞周期中終末停滯且表現(xiàn)出明顯分泌表型的細(xì)胞被稱為衰老細(xì)胞。這些細(xì)胞在腫瘤進(jìn)展中扮演復(fù)雜角色；它們可以根據(jù)疾病階段抑制或促進(jìn)腫瘤生長(zhǎng)。我們開發(fā)了一種小鼠模型，可監(jiān)測(cè)并選擇性消除高表達(dá)細(xì)胞周期依賴性激酶抑制因子p16和白介素-6的細(xì)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(duì)SuSe/PyMT小鼠的功能特征分析證實(shí)，在早期和晚期病變中清除衰老細(xì)胞（衰老細(xì)胞凋亡）分別加速和減緩了腫瘤生長(zhǎng)和轉(zhuǎn)移。腫瘤加速被歸因于免疫抑制性、促腫瘤巨噬細(xì)胞的擴(kuò)增。識(shí)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(xì)胞可以逆轉(zhuǎn)衰老細(xì)胞清除的效應(yīng)，使衰老細(xì)胞凋亡即使在早期階段也具有抗腫瘤效果。我們的結(jié)果表明，靶向免疫抑制性巨噬細(xì)胞可以在減少不良影響的同時(shí)保留衰老細(xì)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(shí)間期卷：Vol 12, Issue 1(2026)

在線時(shí)間：2026年1月1日

DOI：10.1126/sciadv.adx2988

產(chǎn)品信息：

貨號(hào)：C-005

規(guī)格：5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes氯膦酸鹽脂質(zhì)體

辦事處：靶點(diǎn)科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體在小鼠乳腺癌模型清除巨噬細(xì)胞。荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見刊于Science Advances：免疫抑制性巨噬細(xì)胞決定細(xì)胞衰老對(duì)腫瘤進(jìn)展的影響。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)胞的材料和方法：

In vivo cell depletion

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(xiàn)截圖：