肝脏温度升高有效增强人体细胞免疫应答:T细胞活化和可能的单核细胞易位

Increased liver temperature efficiently augments human cellular immune response: T-cell activation and possible monocyte translocation

 

 

抽象

热疗(HT)与其他常规治疗方式相结合,已成为癌症治疗中的一种有前景的方法。除了热诱导的细胞凋亡之外,增强的免疫学效应被认为是对化学疗法或放射疗法的高温治疗的益处。在这里,我们研究了针对肝脏的区域HT对免疫细胞的影响,特别是T细胞和抗原呈递细胞,其在识别和消除肿瘤细胞和病原体如病毒中是重要的。在暴露于这种区域性HT的健康志愿者中,表达活化标记物CD69CD4 +CD8 + T细胞在处理后1小时瞬时增加,随后在处理后6小时降低至基线水平。在处理后24小时,CD69阳性细胞的百分比再次显着增加,但仅在CD8 + T细胞中。 PHA刺激的外周血单核细胞的IFN-γ产生在加热过程后2天逐渐显着增加,在处理后36小时达到峰值。此外,我们发现在治疗后24小时开始IL-1βIL-6的血浆水平显着增加。关于每个白细胞亚群的数量,在高温治疗后1小时观察到单核细胞亚群CD14 + CD16-细胞数量的短暂和显着减少,表明针对肝脏的区域性HT可能具有影响血液单核细胞的外渗。在暴露于肺部或腿部的加热的志愿者中未观察到T细胞活性或单核细胞计数的显着变化。这些结果表明,肝脏的加热可以有效地诱导对肝癌的细胞免疫应答。

 


Increased liver temperature efficiently augments human cellular immune response: T-cell activation and possible monocyte translocation

Yohei KidaSachiyo Tsuji-KawaharaEmail authorValentina OstapenkoSaori KinoshitaEiji KajiwaraHiroyuki KawabataTakae YuasaIwao NishideSusumu YukawaMasakazu IchinoseMasaaki Miyazawa

Abstract
Hyperthermia (HT), in combination with other conventional therapeutic modalities, has become a promising approach in cancer therapy. In addition to heat-induced apoptosis, an augmented immunological effect is considered to be a benefit of hyperthermic treatment over chemo- or radiotherapy. Here, we investigated the effect of regional HT targeting the liver on immune cells, especially T cells and antigen-presenting cells, which are important in recognizing and eliminating tumor cells and pathogens such as viruses. In healthy volunteers exposed to such regional HT, both CD4+ and CD8+ T cells that express an activation marker CD69 increased transiently at 1 h post-treatment, with a subsequent decrease to base levels at 6 h after the treatment. At 24 h post-treatment, the percentage of CD69-positive cells significantly increased again but only among CD8+ T cells. IFN-γ production from PHA-stimulated peripheral blood mononuclear cells was gradually and significantly increased in the 2 days following the heating procedure, peaking at 36 h post-treatment. Furthermore, we found marked increases in plasma levels of IL-1β and IL-6 starting at 24 h post-treatment. With regard to the number of each leukocyte subpopulation, a transient and dramatic decrease in the number of a subset of monocytes, CD14+ CD16− cells, was observed at 1 h after the hyperthermic treatment, suggesting that the regional HT aimed at the liver may have influenced the extravasation of blood monocytes. No significant changes in T-cell activities or monocyte counts were observed in the volunteers exposed to heating of the lungs or the legs. These results suggest that heating of the liver may efficiently induce cellular immune responses to liver cancers.

Cancer Immunology, Immunotherapy
December 2006, Volume 55, Issue 12, pp 1459–1469 | Cite as
https://link.springer.com/article/10.1007%2Fs00262-006-0146-6