目的通过观察磁流体热疗（MFH）联合IL-2对小鼠Lewis肺癌的生长、凋亡及小鼠免疫系统的影响，探讨MFH联合免疫治疗肺癌的可行性。方法建立小鼠浅表Lewis肺癌皮下移植瘤模型，瘤体直径增至0.8cm左右时，将其分为IL-2组、MFH组、MFH+IL-2组及对照组。MFH组瘤体内部注射0.2ml水平约75mg/ml的磁流体，24h后在交变磁场下加温1次，通过控制磁场的强度，加温温度稳定在43.0℃左右30min。IL-2组瘤体内部注射0.2ml（5×104U）的IL-2。MFH+IL-2组热疗后24h，按上述方法向肿瘤内部注射0.2ml（5×104U）的IL-2。对照组瘤体内部注射0.2ml的0.9%氯化钠溶液。采用流式细胞术检测MFH法、MFH+IL-2后小鼠外周血T淋巴细胞亚群的变化。采用免疫组化法检测治疗后肿瘤组织HSP70、CD4+、CD8+等免疫因子的表达，比较MFH组、MFH+IL-2组对肿瘤的治疗效果。结果 MFH组和MFH+IL-2组注射磁流体后肿瘤内部温度迅速升高至43℃，肿瘤细胞呈凋亡和坏死样改变，小鼠外周血T淋巴细胞水平明显升高（P＜0.05），HSP70、CD4+、CD8+水平也均明显升高，小鼠瘤体生长均受到抑制，MFH+IL-2组小鼠瘤体生长抑制更明显。结论43℃、30min条件下的MFH能抑制Lewis肺癌的生长，诱导荷瘤小鼠机体产生抗肿瘤免疫。IL-2单独对荷瘤小鼠肿瘤生长无明显抑制作用，但可以提高外周血CD4+、CD8+水平，从而增强MFH对Lewis肺癌抑瘤效果。%Objective To investigated the combination of magnetic fluid hyperthermia (MFH) with immunotherapy for treatment of Lewis lung carcinoma in mice. Methods The mouse Lewis lung cancer model was induced by subcutaneous infec-tion of tumor cells, the tumor- bearing mice were divided into 4 groups: control group, IL- 2 group, MFH group and MFH+IL- 2 group when the tumor diameter reached 0.8cm. Magnetic fluids were prepared in vitro and directly injected into tumors. Twen-ty- four hours later, the mice were subjected to an alternating magnetic field. The temperature in the tumor was increased to 43.0℃, which was maintained for 30 min with a stable strength of magnetic field. At 24h after MFH, IL- 2 was injected directly into the tumor in MFH+IL- 2 group. Peripheral CD4+ and CD8+ T- lymphocytes were analyzed by flow cytometry, CD4+, CD8+ and HSP70 in tumors were detected by immunohistochemistry staining. Results Combined magnetic fluid hyperthermia and im-munotherapy significantly inhibited the growth of the tumors(P<0.05). Histological analysis demonstrated that the tumor cells un-derwent apoptosis and necrosis, HSP 70, CD4+and CD8+cells were significant increased after treatment (P<0.05). Conclusion Combined magnetic fluid hyperthermia and immunotherapy can improve the therapeutic efficacy for Lewis lung cancer in mice.
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