T cell-NF-κB activation is required for tumor control in vivo.
T cell-NF-κB activation is required for tumor control in vivo.
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DOI：
10.1186/s40425-014-0045-x
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发表时间：
2015
影响因子：
10.9
通讯作者：
Alegre ML
中科院分区：
文献类型：
--
作者：
Barnes SE;Wang Y;Chen L;Molinero LL;Gajewski TF;Evaristo C;Alegre ML
T 细胞具有消除肿瘤的能力，但其消除肿瘤的信号通路尚不完全清楚。 T细胞启动需要激活TCR下游的转录因子AP-1、NFAT和NF-κB，但体内T细胞-NF-κB的激活是否是肿瘤控制所必需的尚不清楚。在肿瘤逐渐生长的人和小鼠中，T 细胞固有的 NF-κB 活性通常会降低。然而，尚不清楚这是否是无法排斥转化细胞的原因，或者是否是肿瘤生长的结果。 T 细胞-NF-κB 对于 T 细胞存活和效应细胞分化很重要，并且在使 T 细胞排斥心脏和胰岛同种异体移植物方面发挥着重要作用，这表明它可能也是消除肿瘤所必需的。在这项研究中，我们测试了正常的 T 细胞-NF-κB 激活对于排斥通常由免疫系统控制生长的肿瘤是否是必需的。 T 细胞-NF-κB 活性遗传受损的小鼠皮下注射 MC57-SIY 肿瘤细胞。随着时间的推移测量肿瘤生长，并使用流式细胞术和细胞因子检测分析评估抗肿瘤免疫反应。尽管肿瘤反应性 T 细胞的积累相同，但 T 细胞-NF-κB 活性受损的小鼠无法排斥野生型小鼠消除的肿瘤。此外，TCR 下游 NF-κB 信号传导的特异性损伤足以防止肿瘤排斥。在T细胞-NF-κB受损的小鼠中，肿瘤抗原特异性T细胞-IFN-γ和TNF-α的产生以及细胞毒性能力均降低，表明该转录因子在肿瘤特异性效应T细胞的效应分化中发挥着重要作用。我们的结果已确定 NF-κB 通路是 T 细胞中重要的信号传导轴，是消除体内生长的肿瘤所必需的。维持或增强 T 细胞-NF-κB 活性可能是抗肿瘤免疫治疗的一个有前景的途径。本文的在线版本 (doi:10.1186/s40425-014-0045-x) 包含补充材料，可供授权用户使用。
T cells have the capacity to eliminate tumors but the signaling pathways by which they do so are incompletely understood. T cell priming requires activation of the transcription factors AP-1, NFAT and NF-κB downstream of the TCR, but whether activation of T cell-NF-κB in vivo is required for tumor control has not been addressed. In humans and mice with progressively growing tumors, the activity of T cell-intrinsic NF-κB is often reduced. However, it is not clear if this is causal for an inability to reject transformed cells, or if it is a consequence of tumor growth. T cell-NF-κB is important for T cell survival and effector differentiation and plays an important role in enabling T cells to reject cardiac and islet allografts, suggesting the possibility that it may also be required for tumor elimination. In this study, we tested whether normal T cell-NF-κB activation is necessary for the rejection of tumors whose growth is normally controlled by the immune system. Mice with genetically impaired T cell-NF-κB activity were subcutaneously injected with MC57-SIY tumor cells. Tumor growth was measured over time, and the anti-tumor immune response was evaluated using flow cytometry and cytokine detection assays. Mice with impaired T cell-NF-κB activity were unable to reject tumors that were otherwise eliminated by wildtype mice, despite equal accumulation of tumor-reactive T cells. In addition, specific impairment of NF-κB signaling downstream of the TCR was sufficient to prevent tumor rejection. Tumor antigen-specific T cell-IFN-γ and TNF-α production, as well as cytotoxic ability, were all reduced in mice with impaired T cell-NF-κB, suggesting an important role for this transcription factor in the effector differentiation of tumor-specific effector T cells. Our results have identified the NF-κB pathway as an important signaling axis in T cells, required for the elimination of growing tumors in vivo. Maintaining or enhancing T cell-NF-κB activity may be a promising avenue for anti-tumor immunotherapy. The online version of this article (doi:10.1186/s40425-014-0045-x) contains supplementary material, which is available to authorized users.
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DOI：
10.1084/jem.185.11.1897
发表时间：
1997-06-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Boothby MR;Mora AL;Scherer DC;Brockman JA;Ballard DW
通讯作者：
Ballard DW
影响因子：
9.8
作者：
Barnes MJ;Krebs P;Harris N;Eidenschenk C;Gonzalez-Quintial R;Arnold CN;Crozat K;Sovath S;Moresco EM;Theofilopoulos AN;Beutler B;Hoebe K
通讯作者：
Hoebe K
DOI：
10.4049/jimmunol.1100845
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kline J;Zhang L;Battaglia L;Cohen KS;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
32.4
作者：
Blonska, Marzenna;Pappu, Bhanu P.;Lin, Xin
通讯作者：
Lin, Xin
影响因子：
8.6
作者：
Broderick, L;Brooks, SP;Bankert, RB
通讯作者：
Bankert, RB