CD91 on dendritic cells governs immunosurveillance of nascent, emerging tumors.

CD91 on dendritic cells governs immunosurveillance of nascent, emerging tumors.
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树突状细胞上的 CD91 控制新生肿瘤的免疫监视。

DOI:
10.1172/jci.insight.127239
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发表时间:
2019
期刊:
影响因子:
8
通讯作者:
Binder,RobertJ
Binder,RobertJ
中科院分区:
医学1区
文献类型:
--
作者:
Sedlacek,AbigailL;Younker,TheodoreP;Zhou,YuJerry;Borghesi,Lisa;Shcheglova,Tatiana;Mandoiu,IonI;Binder,RobertJ

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免疫系统检测异常的癌前细胞,并在癌症发展之前消除它们。包括T细胞在内的免疫细胞已被证明是根除这些异常细胞的关键组成部分,当宿主中缺乏时,癌症的发病率会增加。在这里,我们表明,CD91,一种在抗原呈递细胞上表达的受体,是引发对新生的、新出现的肿瘤的免疫反应所必需的。在不存在CD91的情况下,效应免疫应答被抑制,并且肿瘤发病率和进展被放大。因此,我们还表明,在不存在CD91的情况下产生的肿瘤表达具有指示更大免疫原性的指数的新表位。预期影响配体结合的人CD91中的多态性显示影响癌症患者中的抗肿瘤免疫应答。这项研究提出了一种分子机制,用于引发对新生、新兴肿瘤的免疫反应,成为癌症易感性和进展的预测因子。
The immune system detects aberrant, premalignant cells and eliminates them before the development of cancer. Immune cells, including T cells, have been shown to be critical components in eradicating these aberrant cells, and when absent in the host, incidence of cancer increases. Here, we show that CD91, a receptor expressed on antigen-presenting cells, is required for priming immune responses to nascent, emerging tumors. In the absence of CD91, effector immune responses are subdued, and tumor incidence and progression are amplified. We also show that, consequently, tumors that arise in the absence of CD91 express neo-epitopes with indices that are indicative of greater immunogenicity. Polymorphisms in human CD91 that are expected to affect ligand binding are shown to influence antitumor immune responses in cancer patients. This study presents a molecular mechanism for priming immune responses to nascent, emerging tumors that becomes a predictor of cancer susceptibility and progression.
常见热休克蛋白受体 CD91 在晚期黑色素瘤缓慢进展者的单核细胞上表达上调
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