Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses
Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses
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Dectin-1 对肿瘤细胞的识别协调先天免疫细胞的抗肿瘤反应
DOI：
10.1158/1538-7445.am2015-4056
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发表时间：
2015
期刊：
影响因子：
11.2
通讯作者：
Taniguchi T.
中科院分区：
文献类型：
--
作者：
Ikushima H;Taniguchi T.
癌细胞的根除需要组成复杂免疫系统的细胞之间的通讯。自然杀伤(NK)细胞是免疫系统先天手臂必不可少的肿瘤杀伤效应细胞；然而，关于其他免疫细胞是否或如何识别肿瘤细胞来辅助NK细胞，人们知之甚少。此外，尽管信号转导模式识别受体通过识别病原体相关分子模式(PAMPs)在抵抗入侵病原体的先天免疫反应中发挥重要作用，但这些受体是否以及如何参与抗肿瘤免疫反应仍是一个谜。在这项研究中，我们发现树突状细胞(DC)和巨噬细胞上表达的天然免疫模式识别受体Dectin-1在NK介导的肿瘤细胞杀伤中起关键作用。我们还发现，肿瘤细胞介导的Dectin-1信号是由肿瘤细胞上N-糖链结构的受体识别所激发的，我们称之为肿瘤相关分子模式(TAMPS)。因此，TAMP-Dectin-1信号导致干扰素调节因子5(IRF5)转录因子的激活，并随后诱导NK细胞充分发挥杀伤活性所需的基因。在Dectin-1或IRF5基因缺陷的小鼠中观察到大量肿瘤转移，突显了这些事件的重要性。因此，这些结果揭示了模式识别受体在协调抗肿瘤先天免疫反应中迄今未被识别的一个方面：对TAMPS的识别。这项研究是第一次证明先天性免疫模式识别受体增强了抗肿瘤免疫反应，为天然免疫系统的抗肿瘤活性提供了新的见解，并对抗肿瘤免疫治疗具有意义。引用格式：Hiroaki IKUSHIMA，Tadatsugu Taniguchi。Dectin-1识别肿瘤细胞协调先天免疫细胞进行抗肿瘤反应。[摘要]。见：美国癌症研究协会第106届年会论文集；2015年4月18日至22日，宾夕法尼亚州费城。费城(宾夕法尼亚州)：AACR；癌症资源2015；75(15补充)：摘要编号4056。电话：10.1158-7445
The eradication of cancer cells requires communication between cells which constitute the complex immune system. Natural killer (NK) cells are essential tumor-killing effector cells of the innate arm of the immune system; however, little is known about whether or how other immune cells recognize tumor cells to assist NK cells. In addition, although signal-transducing pattern recognition receptors are known to play important roles in innate immune responses against invading pathogens through recognition of pathogen-associated molecular patterns (PAMPs), it is still enigmatic whether and how these receptors contribute to anti-tumor immune responses. In this study, we show that the innate immune pattern recognition receptor Dectin-1 expressed on dendritic cells (DCs) and macrophages is critical to NK-mediated killing of tumor cells. We also show that tumor cell-mediated Dectin-1 signaling is instigated by the receptor recognition of N-glycan structures on tumor cells, which we term tumor-associated molecular patterns (TAMPs). As such, the TAMP-Dectin-1 signaling causes activation of the Interferon Regulatory Factor 5 (IRF5) transcription factor and subsequent induction of genes required for the full-blown killing activity of NK cells. The importance of these events is underscored by the observation of massive tumor metastasis in mice genetically deficient in either Dectin-1 or IRF5. Thus, these results reveal a hitherto unrecognized facet of pattern recognition receptors in the orchestration of anti-tumor innate immune responses; recognition of TAMPs. This study is the first demonstration that an innate immune pattern recognition receptor potentiates anti-tumor immune responses, offering new insight into anti-tumor activity of the innate immune system with implications for anti-tumor immunotherapy.Citation Format:Hiroaki IKUSHIMA, Tadatsugu TANIGUCHI. Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4056. doi:10.1158/1538-7445.AM2015-4056
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32.4
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