Ostberg Julie R, Repasky Elizabeth A
Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
Cancer Immunol Immunother. 2006 Mar;55(3):292-8. doi: 10.1007/s00262-005-0689-y. Epub 2005 Apr 28.
Elevations in temperature that are associated with inflammation or fever have been linked to improved survival from infections, enhanced immunological functions, and increased control of tumor growth. Over the past few years, several groups have begun to explore the possible linkage among these observations and have tested the hypothesis that various immune cells are especially sensitive to thermal stimulation. However, relatively little is known regarding the effects of thermal stimulation on antigen presenting cells (APCs), such as dendritic cells (DCs). Very recently, several groups have begun to examine the ability of thermal stimuli to regulate the function of these cells which are known to play a pivotal role in the efficacy of vaccines and other immunotherapies. In this review, we summarize what has been discovered about the role of mild thermal stress in regulating various Dendritic cell (DC) activities. Excitingly, it appears that mild elevations of temperature have the potential to enhance antigen uptake, activation associated migration, maturation, cytokine expression and T cell stimulatory activity of DCs. While these studies reveal that the timing, temperature and duration of heating is important, they also set the stage for essential questions that now need to be investigated regarding the molecular mechanisms by which elevated temperatures regulate DC function. With this information, we may soon be able to maximize the strategic use of thermal therapy as an adjuvant, i.e., combining its use with cancer immunotherapies such as vaccines, which depend upon the function of DCs. Several possible strategies and timepoints involving the clinical application of hyperthermia in combination with immunotherapy are presented.
与炎症或发热相关的体温升高已被证明与感染后的生存率提高、免疫功能增强以及肿瘤生长控制增强有关。在过去几年中,几个研究团队开始探索这些观察结果之间的可能联系,并检验了各种免疫细胞对热刺激特别敏感的假设。然而,关于热刺激对抗抗原呈递细胞(APC),如树突状细胞(DC)的影响,我们所知相对较少。最近,几个研究团队开始研究热刺激调节这些细胞功能的能力,已知这些细胞在疫苗和其他免疫疗法的疗效中起关键作用。在这篇综述中,我们总结了关于轻度热应激在调节各种树突状细胞(DC)活性方面所发现的内容。令人兴奋的是,似乎轻度升温有可能增强DC的抗原摄取、激活相关迁移、成熟、细胞因子表达和T细胞刺激活性。虽然这些研究表明加热的时间、温度和持续时间很重要,但它们也为现在需要研究的关于温度升高调节DC功能的分子机制的关键问题奠定了基础。有了这些信息,我们也许很快就能最大限度地将热疗法作为一种辅助手段进行战略应用,即把它与依赖DC功能的癌症免疫疗法(如疫苗)结合使用。本文还介绍了几种可能的策略以及涉及热疗与免疫疗法联合临床应用的时间点。