International Journal of Hyperthermia ( IF 3.1 ) Pub Date : 2021-07-01 , DOI: 10.1080/02656736.2021.1945688 Chao-Chih Wu, Yun-Ting Hsu, Chih-Long Chang
Abstract
Purpose
We aimed to determine the effects and possible mechanisms of hyperthermic intraperitoneal chemotherapy (HIPEC) in targeting ovarian cancer stem-like cells (CSCs).
Methods
Murine ovarian cancer cell lines presenting CSC surface markers were grown intraperitoneally in both immunocompetent and immunodeficient mice, which were then treated by intraperitoneal hyperthermia with the chemotherapeutic agents: paclitaxel and cisplatin. Tumor growth was measured by non-invasive luminescent imaging. Intraperitoneal immune cells, such as CD4+, CD8+ T cells, macrophages, and dendritic cells, were evaluated through flow cytometry analysis.
Results
Combined hyperthermia and chemotherapy exhibited an efficient therapeutic effect in the immunocompetent mice. However, a similar effect was not observed in the immunodeficient mice. Intraperitoneal hyperthermia increased the number of Intraperitoneal macrophages and dendritic cells that were lost due to chemotherapy. Compared with ovarian cancer bulk cells, CSCs were more susceptible to phagocytosis by macrophages.
Conclusion
We demonstrated that the superior therapeutic efficacy and reduced proportion of CSCs associated with intraperitoneal hyperthermic chemotherapy were immune-related. Hyperthermia recruits the phagocytes that target surviving CSCs after chemotherapy. These results provide a novel mechanism for the efficacy of HIPEC in treating ovarian cancer.
中文翻译:
腹腔热灌注化疗通过免疫介导的癌症干细胞靶向增强对卵巢癌的抗肿瘤作用
摘要
目的
我们旨在确定腹腔高温化疗 (HIPEC) 在靶向卵巢癌干细胞样细胞 (CSC) 中的作用和可能机制。
方法
具有 CSC 表面标志物的鼠卵巢癌细胞系在免疫活性小鼠和免疫缺陷小鼠中进行腹膜内生长,然后用化疗药物:紫杉醇和顺铂通过腹膜内热疗进行治疗。通过非侵入性发光成像测量肿瘤生长。通过流式细胞术分析评估腹膜内免疫细胞,例如 CD4 +、CD8 + T 细胞、巨噬细胞和树突细胞。
结果
联合热疗和化疗在免疫活性小鼠中表现出有效的治疗效果。然而,在免疫缺陷小鼠中没有观察到类似的效果。腹腔内热疗增加了因化疗而丢失的腹腔内巨噬细胞和树突状细胞的数量。与卵巢癌大块细胞相比,CSCs 更容易被巨噬细胞吞噬。
结论
我们证明了与腹腔热疗相关的优越治疗效果和降低的 CSC 比例与免疫相关。热疗会招募靶向化疗后存活的 CSC 的吞噬细胞。这些结果为 HIPEC 治疗卵巢癌的疗效提供了新的机制。