利用β-葡聚糖誘導(dǎo)的訓(xùn)練免疫對巨噬細(xì)胞進(jìn)行表觀遺傳和代謝重編程以增強結(jié)直腸癌疫苗反應(yīng)

中文摘要：

結(jié)直腸癌（CRC）對大多數(shù)免疫療法仍具有難治性，癌癥疫苗由于免疫抑制性腫瘤微環(huán)境而失敗。在這里，我們展示了β-葡聚糖誘導(dǎo)的訓(xùn)練免疫通過H3K4me3依賴的表觀遺傳修飾和代謝重編程重塑巨噬細(xì)胞，從而克服這些障礙。在接種了肽包被腺病毒疫苗PeptiCrad的雌性小鼠中，訓(xùn)練增強了糖酵解，肌酸代謝維持CXCL9/10的產(chǎn)生，使巨噬細(xì)胞能夠通過CXCR3招募NK細(xì)胞。反過來，NK細(xì)胞產(chǎn)生CCL5，推動cDC1浸潤和抗原呈遞，這共同增強了效應(yīng)記憶CD8? T細(xì)胞應(yīng)答。此外，在人體外周血單核細(xì)胞和CRC患者衍生的類器官中，訓(xùn)練的巨噬細(xì)胞增強了NK細(xì)胞遷移、抗原特異性T細(xì)胞激活和腫瘤殺傷。這些發(fā)現(xiàn)凸顯了訓(xùn)練免疫作為強效佐劑，以重新激活結(jié)直腸癌疫苗應(yīng)答的潛力。

英文摘要：

Colorectal cancer (CRC) remains refractory to most immunotherapies, with cancer vaccines failing due to an immunosuppressive tumor microenvironment. Here, we show that β-glucan–induced trained immunity overcomes these barriers by reprogramming macrophages through H3K4me3-dependent epigenetic modifications and metabolic rewiring. In female mice vaccinated with peptide-coated adenovirus-based vaccine PeptiCrad, training enhances glycolysis with creatine metabolism sustaining CXCL9/10 production, enabling macrophages to recruit NK cells via CXCR3. In turn, NK cells produce CCL5, driving cDC1 infiltration and antigen presentation, which together amplify effector memory CD8? T cell responses. Moreover, with human peripheral blood mononuclear cells and CRC patient-derived organoids, trained macrophages boost NK migration, antigen-specific T cell activation, and tumor killing. These findings highlight trained immunity as a powerful adjuvant to reinvigorate colorectal cancer vaccination.

論文信息：

論文題目：Leveraging glucan-induced trained immunity for the epigenetic and metabolic rewiring of macrophages to enhance colorectal cancer vaccine response

期刊名稱：Nature Communications

時間期卷：17, Article number: 1757(2026)

在線時間：2026年1月28日

DOI： doi.org/10.1038/s41467-026-68466-5

產(chǎn)品信息：

貨號：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：靶點科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除結(jié)腸癌小鼠腫瘤模型中巨噬細(xì)胞 ，荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見刊于Nature Communications：利用β-葡聚糖誘導(dǎo)的訓(xùn)練免疫對巨噬細(xì)胞進(jìn)行表觀遺傳和代謝重編程以增強結(jié)直腸癌疫苗反應(yīng)。

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

In vivo depletion of specific immune cell types

For macrophage depletion, mice were administered i.p. with 200?µl of chlodronate liposomes (Liposoma, Cat# C-005) 1?day after tumor implantations and then every four days until the end of the experiment. As for NK depletion, mice were treated with 50?μl of anti-Asialo-GM1 antibodies (Purified anti-Asialo-GM1 Antibody, BioLegend, Cat # 146002) day after tumor implantations and given every four days until the end of the experiment. For depletion of both immune population, mice were treated with both treatments 1?day after tumor implanations and given every four days until the end of the experiment. For CD8?+?T cell depletion, mice were given a bolus treatment of 500?µg of anti-CD8 antibody (BioXcell, Cat# #BE0061) given I.P 1 day prior the first PC treatment and was further sustained by injecting 100?µg of anti-CD8 antibody I.P every 3 days.

材料和方法文獻(xiàn)截圖：

研究結(jié)論示意圖：