Suppr超能文献

Fms样酪氨酸激酶3配体对人外周血单核细胞来源树突状细胞和自然杀伤细胞的免疫刺激作用:在卵巢癌治疗中的应用

Immunostimulatory effect of Fms-like tyrosine kinase 3 ligand on peripheral monocyte-derived dendritic cells and natural killer cells: utilization for ovarian cancer treatment.

作者信息

Matsumura Noriomi, Mandai Masaki, Hamanishi Junzo, Yamaguchi Ken, Fukuhara Ken, Yagi Haruhiko, Higuchi Toshihiro, Takakura Kenji, Fujii Shingo

机构信息

Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.

出版信息

Oncol Rep. 2008 Feb;19(2):505-15.

Abstract

Systemic administration of Fms-like tyrosine kinase 3 ligand (FLT3L) has been considered to be a major route of delivery for tumor immunotherapy because expression of its receptor, FLT3, was detected predominantly in hematopoetic progenitor cells. However, several studies indicate that FLT3L locally overexpressed in tumor or dendritic cells (DCs) also shows an anti-tumor effect. In the current study, we found that FLT3 expression is not present in monocytes but is instead induced in DCs through the differentiation process resulting from stimulation by GM-CSF and IL-4. Addition of FLT3L further augmented FLT3 induction and also increased CD40 expression in DCs, leading to enhanced induction of lymphoblastoid cell line-targeted cytotoxic T-lymphocyte response and CD107a mobilization in CD8+ T cells. Furthermore, FLT3L also induced FLT3 expression in peripheral blood NK cells that showed an enhanced response detected by CD107a mobilization. In a murine ovarian cancer model, locally expressed FLT3L showed anti-tumor effects. Collectively, the current study indicates that FLT3L has an immunostimulatory effect on peripheral blood cells and FLT3L targeted to mature peripheral blood cells may serve as a useful tool for cancer immunotherapy.

摘要

Fms样酪氨酸激酶3配体(FLT3L)的全身给药一直被认为是肿瘤免疫治疗的主要给药途径,因为其受体FLT3主要在造血祖细胞中表达。然而,多项研究表明,在肿瘤或树突状细胞(DC)中局部过表达的FLT3L也显示出抗肿瘤作用。在本研究中,我们发现单核细胞中不存在FLT3表达,而是通过GM-CSF和IL-4刺激诱导的分化过程在DC中诱导表达。添加FLT3L进一步增强了FLT3的诱导,并增加了DC中CD40的表达,导致针对淋巴母细胞系的细胞毒性T淋巴细胞反应增强以及CD8+T细胞中CD107a的动员增加。此外,FLT3L还诱导外周血NK细胞中的FLT3表达,通过CD107a动员检测到其反应增强。在小鼠卵巢癌模型中,局部表达的FLT3L显示出抗肿瘤作用。总体而言,本研究表明FLT3L对外周血细胞具有免疫刺激作用,靶向成熟外周血细胞的FLT3L可能成为癌症免疫治疗的有用工具。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验