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鲍曼不动杆菌外膜蛋白A对基于树突状细胞的小鼠黑色素瘤免疫治疗的抗肿瘤活性

Anti-tumor activity of Acinetobacter baumannii outer membrane protein A on dendritic cell-based immunotherapy against murine melanoma.

作者信息

Lee Jun Sik, Kim Jung Wook, Choi Chul Hee, Lee Won Kee, Chung Hae Young, Lee Je Chul

机构信息

Department of Microbiology, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.

出版信息

J Microbiol. 2008 Apr;46(2):221-7. doi: 10.1007/s12275-008-0052-z. Epub 2008 Jun 11.

DOI:10.1007/s12275-008-0052-z
PMID:18545973
Abstract

Acinetobacter baumannii outer membrane protein A (AbOmpA) is a major surface protein that is an important pathogen-associated molecular pattern. Based on our previous findings that AbOmpA induced the phenotypic maturation of dendritic cells (DCs) and drove the Th1 immune response in vitro, we investigated the therapeutic efficacy of AbOmpA-pulsed DC vaccines in a murine melanoma model. The surface expression of co-stimulatory molecules (CD80 and CD86) and major histocompatibility complex class I and II molecules was higher in DCs pulsed with AbOmpA alone or with a combination of B16F10 cell lysates than that of DCs pulsed with B16F10 cell lysates. AbOmpA stimulated the maturation of murine splenic DCs in vivo. In a therapeutic model of murine melanoma, AbOmpA-pulsed DCs significantly retarded tumor growth and improved the survival of tumor-bearing mice. AbOmpA-pulsed DCs significantly enhanced CD8+, interleukin-2+ T cells and CD4+, interferon-gamma+ T cells in tumor-bearing mice. These results provide evidence that AbOmpA may be therapeutically useful in adjuvant DC immunotherapy against poorly immunogenic melanoma without tumor-specific antigens.

摘要

鲍曼不动杆菌外膜蛋白A(AbOmpA)是一种主要的表面蛋白,是一种重要的病原体相关分子模式。基于我们之前的发现,即AbOmpA在体外诱导树突状细胞(DCs)的表型成熟并驱动Th1免疫反应,我们在小鼠黑色素瘤模型中研究了AbOmpA脉冲DC疫苗的治疗效果。单独用AbOmpA或与B16F10细胞裂解物组合脉冲的DCs中,共刺激分子(CD80和CD86)以及主要组织相容性复合体I类和II类分子的表面表达高于用B16F10细胞裂解物脉冲的DCs。AbOmpA在体内刺激小鼠脾脏DCs的成熟。在小鼠黑色素瘤的治疗模型中,AbOmpA脉冲DCs显著延缓肿瘤生长并提高荷瘤小鼠的生存率。AbOmpA脉冲DCs显著增强荷瘤小鼠中的CD8 +、白细胞介素-2 + T细胞和CD4 +、干扰素-γ + T细胞。这些结果提供了证据,表明AbOmpA在针对无肿瘤特异性抗原的低免疫原性黑色素瘤的辅助DC免疫治疗中可能具有治疗作用。

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