摘要
CD40是属于肿瘤坏死因子超家族成员的共刺激分子,并在树突状细胞的活化中是必不可少的。树突细胞(DCs)是抗原呈递细胞,能够激活T淋巴细胞对癌症细胞的免疫应答。尽管其在癌症免疫治疗中的重要意义,但是对于癌症中DCs特征,特别是其CD40的表达特征的研究很少。我们回顾了不同癌症中DCs细胞的CD40表达的可用的数据,和其在癌症免疫治疗中的应用。通过参照系统评价和meta分析(PRISMA)的最优报告条目对癌症DCs细胞中CD40的表达进行系统的综述,从927条研究中符合纳入排除标准的有21条。癌症的不同类型和状态,DCs的不同来源以及CD40表达的检测方法上的差别导致了截然不同的研究结果。在肿瘤浸润的DCs细胞(tiDCs),来源于体外培养的使用细胞因子刺激的血单核细胞DCs细胞(MoDCs)和体外暴露于肿瘤细胞的DCs细胞通常表达较低的CD40;这些研究显示在癌症特别是迁移性疾病中DCs细胞的CD40表达水平受损。但是,在某些癌症病人新鲜的外周血单核细胞(PBMC)中鉴定的DCs细胞有高数量的CD40表达阳性细胞,这可能是因为肿瘤衍生因子对DCs的局部刺激导致。这些结果提供的证据表明一些癌症病人可能表现有部分系统的DC活化和CD40表达增加来响应肿瘤的出现,但是这种活性可能因为肿瘤产生的因子的存在而被消除。这个评述鉴定了不同癌症中DCs细胞CD40表达的核心论文,并讨论了这些研究与方法学差异相关的局限性和结果的差异性。这些结果强调有必要对CD40-CD40配体通路在传达癌症治疗中的作用进行深入研究。
关键词: 抗原呈递细胞,癌症,CD40,CD40配体,树突细胞,免疫治疗
图形摘要
Current Cancer Drug Targets
Title:The Role of CD40 Expression in Dendritic Cells in Cancer Biology; A Systematic Review
Volume: 14 Issue: 7
关键词: 抗原呈递细胞,癌症,CD40,CD40配体,树突细胞,免疫治疗
摘要: CD40 is a co-stimulatory molecule belonging to the tumor necrosis factor superfamily and is essential in activation of dendritic cells. Dendritic cells (DCs) are antigen-presenting cells capable of initiating cytotoxic T-lymphocyte immune response against cancer cells. However, there are few studies on the characterization of DCs in cancer, specifically their expression of CD40, despite its implication in cancer immunotherapy. We reviewed available data on the expression of CD40 on DCs in various cancers, and its implications for cancer immunotherapy.
A systematic review on CD40 expression on DCs in cancer was performed with reference to preferred reporting items for systematic reviews and meta-analyses (PRISMA). Studies that satisfied the inclusion and exclusion criteria were 21 out of 927.
Variations in type and status of the cancers, source of DCs and methodology for detecting CD40 expression amongst the studies resulted in contrasting results. DCs generally expressed low CD40 in tumor infiltrating DCs (tiDCs), in DCs derived by in vitro culture from blood monocytes using cytokine stimulation (MoDCs) and in DCs exposed in vitro to tumor cells lines; the studies suggested that CD40 expression in DCs is impaired in cancer particularly in metastatic disease. However, DCs identified in fresh peripheral blood mononuclear cells (PBMC) expressed higher numbers of CD40 positive cells in some cancer patients, which could be due to tumor-derived factors leading to partially-stimulated DCs. The results provide evidence that some cancer patients may show partial systemic DC activation and expression of increased CD40 in response to the presence of tumor but that such activity may become abortive in the presence of factors produced by the tumor.
This review has thus identified key papers on CD40 expression on DCs in various cancers and discusses the limitations and contrasting results of these studies in relation to variations in methodology. The results highlight the need for further studies on the role of CD40-CD40 ligand pathway to inform cancer treatment.
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Cite this article as:
The Role of CD40 Expression in Dendritic Cells in Cancer Biology; A Systematic Review, Current Cancer Drug Targets 2014; 14 (7) . https://dx.doi.org/10.2174/1568009614666140828103253
DOI https://dx.doi.org/10.2174/1568009614666140828103253 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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