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目的观察不同加热温度及联合免疫佐剂对大鼠Walker-256肿瘤生长及CD4+T细胞和CD8+T细胞表达的影响。方法建立大鼠双侧腋下皮下移植Walker-256肿瘤模型,接种后7d随机分成6组:Ⅰ组(单纯植入热籽对照);Ⅱ组(42～46℃单纯热疗);Ⅲ组(42～46℃热疗+免疫佐剂);Ⅳ组(50～55℃单纯热疗);Ⅴ组(50～55℃热疗+免疫佐剂);Ⅵ组(单纯免疫佐剂对照)。每3d测双侧肿瘤大小的变化,治疗后14d取肿瘤组织行HE染色,免疫组织化学方法检测肿瘤组织CD8+T细胞的表达,免疫荧光法检测CD4+T细胞的表达。结果热疗后14d,Ⅱ、Ⅲ、Ⅳ、Ⅴ组两侧肿瘤体积均有不同程度缩小,Ⅴ组治疗侧及对侧肿瘤体积分别缩小34.6%、60.1%,并有3只大鼠对侧肿瘤完全消退,与Ⅰ组、Ⅵ组2个对照组比较,有显著性差异(q=4.552,P<0.05;q=4.400,P<0.05)。组织学检查肿瘤细胞呈凋亡、坏死性改变,伴大量淋巴细胞浸润,V组还可见大量吞噬细胞,对侧未见明显坏死肿瘤细胞,淋巴细胞浸润较明显。免疫学检查加热后CD4+T细胞和CD8+T细胞较对照组(Ⅰ、Ⅵ组)明显增多,差异具有显著性(P<0.05),其中均以V组表达最多(P<0.05)。结论50～55℃瘤内局部加热不仅能抑制乳腺癌生长,还可增强机体的细胞免疫功能并具有异位效应,免疫佐剂能增强其抑瘤作用及异位效应。
Objective To observe the effect of different heating temperature and adjuvant on the Walker-256 tumor growth and the expression of CD4 + T cells and CD8 + T cells in rats. Methods Walker-256 tumor model was established in both sides of subcutaneous axillary subcutaneous transplantation in rats. The rats were randomly divided into 6 groups at 7 days after inoculation: group Ⅰ (heat implanted seeds alone); group Ⅱ (hyperthermia at 42 ~ 46 ℃); group Ⅲ 42 ~ 46 ℃ hyperthermia + adjuvant); Group Ⅳ (50 ~ 55 ℃ hyperthermia); Group V (50 ~ 55 ℃ hyperthermia + adjuvant); Tumor size was measured every three days. The tumors were stained with HE at 14 days after treatment. The expression of CD8 + T cells was detected by immunohistochemistry and the expression of CD4 + T cells by immunofluorescence. Results On the 14th day after hyperthermia, the volume of tumor on both sides of group Ⅱ, Ⅲ, Ⅳ and Ⅴ decreased to some extent. The volume of the treated side and the contralateral group of Ⅴ reduced 34.6% and 60.1% respectively, and there were 3 contralateral tumors Completely disappeared. Compared with the two control groups in group Ⅰ and group Ⅵ, there was a significant difference (q = 4.552, P <0.05; q = 4.400, P <0.05). Histological examination of tumor cells showed apoptosis, necrosis changes, with a large number of lymphocytic infiltration, V group also found a large number of phagocytic cells, contralateral no obvious necrosis of tumor cells, lymphocyte infiltration more obvious. After immunization, CD4 + T cells and CD8 + T cells increased significantly (P <0.05) compared with control group (Group Ⅰ and Ⅵ), and were most expressed in group V (P <0.05). Conclusion Local heating in the tumor at 50-55 ℃ can not only inhibit the growth of breast cancer, but also enhance the cellular immune function and have the ectopic effect. The immune adjuvant can enhance its anti-tumor effect and ectopic effect.