首页|GRA15Ⅱ在小鼠肿瘤微环境中促进巨噬细胞极化抗肝癌

GRA15Ⅱ在小鼠肿瘤微环境中促进巨噬细胞极化抗肝癌

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肿瘤相关巨噬细胞(TAM)与肿瘤的转归密切相关,探索刚地弓形虫致密颗粒蛋白分子(GRA15Ⅱ)在肿瘤微环境中通过诱导巨噬细胞(Mφ)极化抑制肿瘤生长的作用机制。通过构建肝细胞癌小鼠,注射LV-gra15Ⅱ重组慢病毒后,采用实时荧光定量PCR、酶联免疫法、免疫组化、流式细胞术和共聚焦显微镜分析肿瘤微环境中的免疫应答情况。结果显示,GRA15Ⅱ可在体外诱导M2样Mφ向M1表型偏移。而且,在荷瘤小鼠注射LV-gra15Ⅱ后,肿瘤体积明显减小,进一步分析发现,在肿瘤微环境中GRA15Ⅱ主要通过TRAF6途径激活NF-κB,诱导TAM从M2向M1偏移,且NO、IL-12、TNF-α的表达上调,发挥Th1免疫应答。GRA15Ⅱ能够抑制肿瘤生长,此研究为肿瘤免疫治疗提供新的思路和策略,为开发新的药物提供实验室基础。
GRA15Ⅱ Against Hepatic Carcinoma in Mice via Promotion of Macrophage Polarization in Tumor Microenvironment
Tumor-associated macrophages(TAMs)play an important role in the development of tumors.The aim of the present study was to investigate the role of the dense granule protein molecule of Toxoplasma gondii(GRA15Ⅱ)in inhibition of the tumor growth via macrophage polarization.Here,we constructed a recombinant LV-GRA15n and injected it into tumor bearing C57BL/6 mice for analyzing the immune responses in tumor microenvironment by RT-PCR,ELISA,IHC,FCM and LSCM.GRA15Ⅱ induced the repolarization of M2-like macrophages without affecting the M1 phenotype in vitro.Additionally,GRA15Ⅱ inhibited the tumor growth and induced the TAM polarization from M2-like to M1-like by TRAF6-NF-κB pathway activation.Furthmore,expression of NO,IL-12 and TNF-α was upregulated to enhance Th1 immune response in the tumor microenvironment.In conclusion,GRA15Ⅱ inhibited the tumor growth,which might lead to new immunotherapy strategies and experimental research for the development of new drugs to tumor treatment.

Toxoplasma gondiidense granule proteinhepatocellular carcinomasmacrophagespolarization

余焱霞、张远、王艳玲、蔡亦红

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安徽医科大学公共卫生学院卫生检验与检疫,合肥 230032

安徽医科大学病原生物学安徽省重点实验室,合肥 230032

安徽医科大学人畜共患病安徽高校省级重点实验室,合肥 230032

弓形虫 致密颗粒蛋白 肝细胞癌 巨噬细胞 极化

国家自然科学基金

81572801

2024

中国动物传染病学报
中国农业科学院上海兽医研究所

中国动物传染病学报

CSTPCD北大核心
影响因子:0.651
ISSN:1674-6422
年,卷(期):2024.32(1)
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