中文摘要：
在胰腺导管腺癌（PDAC）中，促纤维增生性基质与免疫抑制性肿瘤微环境（TME）构成了免疫治疗的屏障。本研究证实，MG53（TRIM72）是决定巨噬细胞命运与抗肿瘤免疫的关键调控因子；髓系特异性敲除 MG53 会将巨噬细胞锁定于抑制表型，进而加速胰腺导管腺癌进展，而恢复 MG53 表达则可解除肿瘤微环境的免疫抑制。机制层面，MG53 结合*Irf7*基因座，抑制促肿瘤髓系细胞程序；同时敲除 IRF7 可逆转 MG53 缺陷模型的表型。临床研究显示，肿瘤相关巨噬细胞（TAM）的**MG53 低表达 / IRF7 高表达**特征，在多种胃肠道恶性肿瘤中均与生存期缩短相关，在胰腺导管腺癌队列中尤为显著。本研究利用巨噬细胞靶向的 mRNA-LNP 平台在体内恢复 MG53 表达，能够抑制胰腺导管腺癌肿瘤生长并增强抗肿瘤免疫活性。本研究结果表明，MG53 可作为髓系检查点调控分子，提示基于 mRNA 的细胞重编程策略有望用于克服胰腺导管腺癌的治疗耐药。
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.
论文信息：
论文题目：MG53 suppresses IRF7 to reprogram macrophages and promote antitumor immunity in pancreatic ductal adenocarcinoma
期刊名称：Cell Reports
时间期卷：Volume 45, Issue 10, 118000
Doi： 10.1016/j.celrep.2026.118000
产品信息：
货号：CP-010-010
规格：10ml+10ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体清除胰腺导管腺癌（PDAC）小鼠KPC模型，荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Cell Reports：MG53 通过抑制 IRF7 重编程巨噬细胞，进而促进胰腺导管腺癌的抗肿瘤免疫。
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：
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.
巨噬细胞清除材料和方法文献截图：
