Effector CD8+ T cell IFN-γ production and cytotoxicity are enhanced by mild hyperthermia.
Effector CD8+ T cell IFN-γ production and cytotoxicity are enhanced by mild hyperthermia.
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DOI：
10.3109/02656736.2011.616182
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Repasky EA
中科院分区：
文献类型：
--
作者：
Mace TA;Zhong L;Kokolus KM;Repasky EA
临床试验结合热疗与放疗和/或化疗的癌症治疗，导致改善总体生存和控制局部复发。热增强的抗免疫功能在这些影响中的贡献是相当大的兴趣，但不理解;需要研究高温对免疫效应细胞的基本影响。本研究的目的是研究轻度高温对肿瘤抗原特异性（Ag）效应CD 8 + T细胞功能的影响。将Pmel-1 Ag特异性CD 8 + T细胞暴露于轻度高温，并测试IFN-γ产生和细胞毒性的变化。此外，还研究了热处理后的整体质膜组织和信号蛋白的磷酸化。与使用较低温度（33和37°C）观察到的相比，将效应子Pmel-1特异性CD 8 + T细胞暴露于轻度高温（39.5°C）导致Ag特异性IFN-γ产生和肿瘤靶细胞杀伤显著增强。此外，在高温期间抑制蛋白质合成不会减少随后Ag诱导的CD 8 + T细胞产生IFN-γ。与这些效应相关的是，我们观察到GM 1+脂质微区在质膜上的明显聚集以及LAT和PKCθ磷酸化的增强，这可能与观察到的轻度高温后Ag特异性效应CD 8 + T细胞IFN-γ基因转录的增强有关。然而，有丝分裂原介导的IFN-γ的产生（其绕过抗原对T细胞受体的活化）并未增强。轻度高热后抗原依赖性效应T细胞活性增强。这些影响可能发生在接受热疗法治疗的患者中。这些数据还为使用热疗法作为免疫疗法的佐剂以改善CD 8+效应细胞功能提供了支持。
Clinical trials combining hyperthermia with radiation and/or chemotherapy for cancer treatment have resulted in improved overall survival and control of local recurrences. The contribution of thermally enhanced anti-immune function in these effects is of considerable interest, but not understood; studies on the fundamental effects of elevated temperature on immune effector cells are needed. The goal of this study is to investigate the potential of mild hyperthermia to impact tumor antigen-specific (Ag) effector CD8+ T cell functions. Pmel-1 Ag-specific CD8+ T cells were exposed to mild hyperthermia and tested for changes in IFN-γ production and cytotoxicity. Additionally, overall plasma membrane organization and the phosphorylation of signaling proteins were also investigated following heat treatment. Exposing effector Pmel-1 specific CD8+ T cells to mild hyperthermia (39.5°C) resulted in significantly enhanced Ag-specific IFN-γ production and tumor target cell killing compared to that seen using lower temperatures (33 and 37°C). Further, inhibition of protein synthesis during hyperthermia did not reduce subsequent Ag-induced IFN-γ production by CD8+ T cells. Correlated with these effects, we observed a distinct clustering of GM1+ lipid microdomains at the plasma membrane and enhanced phosphorylation of LAT and PKCθ which may be related to an observed enhancement of Ag-specific effector CD8+ T cell IFN-γ gene transcription following mild hyperthermia. However, mitogen–mediated production of IFN-γ, which bypasses T cell receptor activation with antigen, was not enhanced. Antigen-dependent effector T cell activity is enhanced following mild hyperthermia. These effects could potentially occur in patients being treated with thermal therapies. These data also provide support for the use of thermal therapy as an adjuvant for immunotherapies to improve CD8+ effector cell function.
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影响因子：
5.8
作者：
Diederichsen, ACP;Hjelmborg, JV;Fenger, C
通讯作者：
Fenger, C
影响因子：
4.4
作者：
Huang, Shih-Chia;Tsai, Hwei-Fang;Hsu, Ping-Ning
通讯作者：
Hsu, Ping-Ning
影响因子：
51.1
作者：
Issels, Rolf D.;Lindner, Lars H.;Verweij, Jaap;Wust, Peter;Reichardt, Peter;Schem, Baard-Christian;Abdel-Rahman, Sultan;Daugaard, Soeren;Salat, Christoph;Wendtner, Clemens-Martin;Vujaskovic, Zeljko;Wessalowski, Ruediger;Jauch, Karl-Walter;Duerr, Hans Roland;Ploner, Ferdinand;Baur-Melnyk, Andrea;Mansmann, Ulrich;Hiddemann, Wolfgang;Blay, Jean-Yves;Hohenberger, Peter
通讯作者：
Hohenberger, Peter
影响因子：
3.1
作者：
DATTA, NR;BOSE, AK;GUPTA, S
通讯作者：
GUPTA, S
影响因子：
4.4
作者：
Cippitelli, M;Fionda, C;Santoni, A
通讯作者：
Santoni, A