中文摘要：

在胰腺導管腺癌（PDAC）中，促纖維增生性基質與免疫抑制性腫瘤微環境（TME）構成了免疫治療的屏障。本研究證實，MG53（TRIM72）是決定巨噬細胞命運與抗腫瘤免疫的關鍵調控因子；髓系特異性敲除 MG53 會將巨噬細胞鎖定于抑制表型，進而加速胰腺導管腺癌進展，而恢復 MG53 表達則可解除腫瘤微環境的免疫抑制。機制層面，MG53 結合*Irf7*基因座，抑制促腫瘤髓系細胞程序；同時敲除 IRF7 可逆轉 MG53 缺陷模型的表型。臨床研究顯示，腫瘤相關巨噬細胞（TAM）的**MG53 低表達 / IRF7 高表達**特征，在多種胃腸道惡性腫瘤中均與生存期縮短相關，在胰腺導管腺癌隊列中尤為顯著。本研究利用巨噬細胞靶向的 mRNA-LNP 平臺在體內恢復 MG53 表達，能夠抑制胰腺導管腺癌腫瘤生長并增強抗腫瘤免疫活性。本研究結果表明，MG53 可作為髓系檢查點調控分子，提示基于 mRNA 的細胞重編程策略有望用于克服胰腺導管腺癌的治療耐藥。

英文摘要：

In pancreatic ductal adenocarcinoma (PDAC), the desmoplastic stroma and immunosuppressive tumor microenvironment (TME) present barriers to immunotherapy. Here, we show that MG53 (TRIM72) is a critical regulator of macrophage fate and anti-tumor immunity; its myeloid-specific depletion accelerates PDAC progression by locking macrophages into a suppressive state, whereas its restoration dismantles the immunosuppressive TME. Mechanistically, MG53 binds the Irf7 locus to suppress the pro-tumorigenic myeloid program, and concomitant IRF7 deletion reverses the phenotype of MG53-deficient models. Clinically, an MG53-low/IRF7-high TAM signature correlates with reduced survival across gastrointestinal malignancies, particularly within PDAC cohorts. Using a macrophage-tropic mRNA-LNP platform to restore MG53 expression in vivo, thereby suppressing tumor growth and enhancing antitumor immune activity in PDAC. Our findings demonstrate that MG53 functions as a myeloid checkpoint regulator and suggest mRNA-based reprogramming as a potential strategy to address therapeutic resistance in PDAC.

論文信息：

論文題目：MG53 suppresses IRF7 to reprogram macrophages and promote antitumor immunity in pancreatic ductal adenocarcinoma

期刊名稱：Cell Reports

時間期卷：Volume 45, Issue 10, 118000

Doi： 10.1016/j.celrep.2026.118000 External Link

產品信息：

貨號：CP-010-010

規格：10ml+10ml

品牌：Liposoma

產地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點科技

Clodronate Liposomes氯膦酸鹽脂質體清除胰腺導管腺癌（PDAC）小鼠KPC模型，荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Cell Reports：MG53 通過抑制 IRF7 重編程巨噬細胞，進而促進胰腺導管腺癌的抗腫瘤免疫。

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：

In vivo macrophage depletion

Subcutaneous inject MC38 cells on day 0, and intraperitoneal injected IgG1 (Bio X Cell, #BE0088) or anti-mouse CSF1 (Bio X Cell, #BE0204) 20mg kg?1 on day 3 and day 6. Control group mice were intraperitoneal injected with 200 μL PBS. Clodronate liposomes and control liposomes (Liposoma, #CP-010–010) were injected i.p. 200 μL on day 0, day 7 and day 14 after tumor cells inoculation.

巨噬細胞清除材料和方法文獻截圖：