Type I interferon is selectively required by dendritic cells for immune rejection of tumors.
Type I interferon is selectively required by dendritic cells for immune rejection of tumors.
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DOI：
10.1084/jem.20101158
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发表时间：
2011-09-26
期刊：
影响因子：
--
通讯作者：
Schreiber RD
中科院分区：
文献类型：
--
作者：
Diamond MS;Kinder M;Matsushita H;Mashayekhi M;Dunn GP;Archambault JM;Lee H;Arthur CD;White JM;Kalinke U;Murphy KM;Schreiber RD
树突状细胞对I型干扰素的反应性是产生抗肿瘤T细胞反应和肿瘤排斥反应所必需的。癌症免疫编辑是免疫系统抑制肿瘤生长并塑造肿瘤免疫原性的过程。我们以前报道过，I型干扰素(α/β)在这一过程中起着核心作用，而造血细胞是I型干扰素作用的关键靶点。然而，干扰素-α/β影响的特定细胞和I型干扰素诱导的功能过程仍然不清楚。在这里，我们表明，I型干扰素是启动抗肿瘤反应所必需的，在癌症免疫编辑过程中，它的作用与干扰素-γ在时间上是不同的。利用混合骨髓嵌合小鼠，我们证明了I型干扰素在先天免疫间隔内的选择性敏感性对于肿瘤特异性T细胞的启动和肿瘤的清除是必不可少的。我们进一步表明，在树突状细胞(DC；Itgax-Cre+Ifnar1f/f小鼠)中缺乏IFNAR1(干扰素-α/β受体1)的小鼠不能排斥高免疫原性的肿瘤细胞，并且这些小鼠的α+DC在与CD8+T细胞的抗原交叉呈递方面存在缺陷。相比之下，NK细胞耗尽的小鼠或粒细胞和巨噬细胞群中缺乏IFNAR1的小鼠通常会排斥这些肿瘤。因此，DC，特别是CD8α+DC在淋巴细胞介导的肿瘤排斥反应中是内源性I型干扰素的功能相关靶点。
Dendritic cell responsiveness to type I interferon is required for the generation of antitumor T cell responses and tumor rejection. Cancer immunoediting is the process whereby the immune system suppresses neoplastic growth and shapes tumor immunogenicity. We previously reported that type I interferon (IFN-α/β) plays a central role in this process and that hematopoietic cells represent critical targets of type I IFN’s actions. However, the specific cells affected by IFN-α/β and the functional processes that type I IFN induces remain undefined. Herein, we show that type I IFN is required to initiate the antitumor response and that its actions are temporally distinct from IFN-γ during cancer immunoediting. Using mixed bone marrow chimeric mice, we demonstrate that type I IFN sensitivity selectively within the innate immune compartment is essential for tumor-specific T cell priming and tumor elimination. We further show that mice lacking IFNAR1 (IFN-α/β receptor 1) in dendritic cells (DCs; Itgax-Cre+Ifnar1f/f mice) cannot reject highly immunogenic tumor cells and that CD8α+ DCs from these mice display defects in antigen cross-presentation to CD8+ T cells. In contrast, mice depleted of NK cells or mice that lack IFNAR1 in granulocytes and macrophage populations reject these tumors normally. Thus, DCs and specifically CD8α+ DCs are functionally relevant targets of endogenous type I IFN during lymphocyte-mediated tumor rejection.
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影响因子：
20.3
作者：
Kamphuis, Elisabeth;Junt, Tobias;Kalinke, Ulrich
通讯作者：
Kalinke, Ulrich
影响因子：
30.5
作者：
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影响因子：
158.5
作者：
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影响因子：
3
作者：
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通讯作者：
Förster, I
影响因子：
32.4
作者：
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通讯作者：
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