Old and new facts about hyperthermia-induced modulations of the immune system
Old and new facts about hyperthermia-induced modulations of the immune system
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DOI：
10.3109/02656736.2012.677933
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发表时间：
2012-01-01
影响因子：
3.1
通讯作者：
Gaipl, Udo S.
中科院分区：
文献类型：
--
作者：
Frey, Benjamin;Weiss, Eva-Maria;Gaipl, Udo S.
热疗（HT）是放疗（RT）和化疗（CT）的有效增敏剂，已被证明可直接或间接调节先天性和适应性免疫系统的细胞。我们将集中在这篇文章中如何抗肿瘤免疫可以诱导HT。与一些体外试验相反，体内检查表明，HT直接激活自然杀伤细胞和吞噬细胞（如粒细胞）对抗肿瘤。由于热也激活树突状细胞（DC），HT应与进一步的死亡刺激（RT，CT或免疫治疗）相结合，以分配肿瘤抗原，来源于，例如，坏死的肿瘤细胞，由DC摄取。我们将概述HT结合其他疗法诱导免疫原性肿瘤细胞和直接杀死肿瘤细胞有助于对肿瘤的免疫激活。研究表明，HT对免疫细胞的非有益作用大多是及时限制的。一个特别的重点是设置在免疫激活介导的细胞外存在的热休克蛋白（HSP）携带肿瘤抗原和死亡的肿瘤细胞释放进一步的危险信号。除了进一步的应激刺激，局部HT治疗发挥远位效应，并可能被认为是原位肿瘤疫苗接种。在患者中观察到自然杀伤（NK）细胞活性增加、淋巴细胞浸润和HSP介导的免疫原性肿瘤细胞诱导。因此，添加HT的治疗可以被认为是一种个性化的癌症治疗方法，通过特异性激活针对个体独特肿瘤的免疫系统。
Hyperthermia (HT) is a potent sensitiser for radiotherapy (RT) and chemotherapy (CT) and has been proven to modulate directly or indirectly cells of the innate and adaptive immune system. We will focus in this article on how anti-tumour immunity can be induced by HT. In contrast to some in vitro assays, in vivo examinations showed that natural killer cells and phagocytes like granulocytes are directly activated against the tumour by HT. Since heat also activates dendritic cells (DCs), HT should be combined with further death stimuli (RT, CT or immune therapy) to allocate tumour antigen, derived from, for example, necrotic tumour cells, for uptake by DCs. We will outline that induction of immunogenic tumour cells and direct tumour cell killing by HT in combination with other therapies contributes to immune activation against the tumour. Studies will be presented showing that non-beneficial effects of HT on immune cells are mostly timely restricted. A special focus is set on immune activation mediated by extracellular present heat shock proteins (HSPs) carrying tumour antigens and further danger signals released by dying tumour cells. Local HT treatment in addition to further stress stimuli exerts abscopal effects and might be considered as in situ tumour vaccination. An increased natural killer (NK) cell activity, lymphocyte infiltration and HSP-mediated induction of immunogenic tumour cells have been observed in patients. Treatments with the addition of HT therefore can be considered as a personalised cancer treatment approach by specifically activating the immune system against the individual unique tumour.