Graduate Institute of Mechanical and Electrical Engineering, National Taipei University of Technology, Taipei City, Taiwan.
PLoS One. 2013 Jul 23;8(7):e69336. doi: 10.1371/journal.pone.0069336. Print 2013.
The purpose of this study was to investigate the anti-tumor effect and potential mechanisms of i.p. hyperthermia in combination with α-galactosylceramide (α-GalCer) for the treatment of ovarian cancer. In this study, immuno-competent tumor models were established using murine ovarian cancer cell lines and treated with i.p. hyperthermia combining α-GalCer. Th1/Th2 cytokine expression profiles in the serum, NK cell cytotoxicity and phagocytic activities of dendritic cells (DCs) were assayed. We also analyzed the number of CD8(+)/IFN-γ(+) tumor specific cytotoxic T cells, as well as the tumor growth based on depletion of lymphocyte sub-population. Therapeutic effect on those ovarian tumors was monitored by a non-invasive luminescent imaging system. Intra-peritoneal hyperthermia induced significant pro-inflammatory cytokines expression, and sustained the response of NK and DCs induced by α-GalCer treatment. The combination treatment enhanced the cytotoxic T lymphocyte (CTL) immune response in two mouse ovarian cancer models. This novel treatment modality by combination of hyperthermia and glycolipid provides a pronounced anti-tumor immune response and better survival. In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. Both innate and adaptive immunities were involved and resulted in a superior therapeutic effect in treating the ovarian cancer.
本研究旨在探讨腹腔内高热联合α-半乳糖神经酰胺（α-GalCer）治疗卵巢癌的抗肿瘤作用及其潜在机制。本研究采用小鼠卵巢癌细胞系建立免疫功能正常的肿瘤模型，并采用腹腔内高热联合α-GalCer 进行治疗。检测血清中 Th1/Th2 细胞因子表达谱、NK 细胞的细胞毒性和树突状细胞（DC）的吞噬活性。我们还分析了 CD8(+)/IFN-γ(+)肿瘤特异性细胞毒性 T 细胞的数量，以及基于淋巴细胞亚群耗竭的肿瘤生长情况。通过非侵入性发光成像系统监测这些卵巢肿瘤的治疗效果。腹腔内热疗诱导产生明显的促炎细胞因子表达，并维持α-GalCer 治疗诱导的 NK 和 DC 的反应。联合治疗增强了两种小鼠卵巢癌模型中的细胞毒性 T 淋巴细胞（CTL）免疫反应。这种新型的联合热疗和糖脂治疗方式可引起强烈的抗肿瘤免疫反应，从而提高生存率。总之，腹腔内热疗增强了 α-GalCer 刺激的 DC 产生的促炎细胞因子分泌和吞噬活性。随后，通过与腹腔内热疗联合，进一步增强了由 α-GalCer 诱导的 CTL 免疫反应。先天免疫和适应性免疫均参与其中，从而在治疗卵巢癌方面取得了更好的疗效。
