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目的探讨CD80、CD86和CD137L基因联合表达对肿瘤免疫原性的影响。方法按接种变异瘤株不同,将BAL B／c小鼠随机分成A组(H22-Wt细胞)、B组(H22-neo细胞)、C组(H22- CD80／CD86+细胞)、D组(H22-CD137L+细胞)、E组(H22-CD80／CD86／CD137L+细胞)5组,建立H22-BAL B／c小鼠荷肝癌模型,A、B组为对照组。观察小鼠成瘤率、成瘤潜伏期、荷瘤鼠存活率及肿瘤增殖情况。通过复种试验观察转基因对H22变异株免疫原性和机体免疫保护作用的影响。结果E组首次接种成瘤率仅有50．0％,显著低于其余4组(P<0．01)。首次接种后,C组荷瘤鼠肿瘤生长受到明显抑制,有2只荷瘤鼠肿瘤完全消退。E组肿瘤生长所受抑制较C组更为明显,肿瘤峰值体积显著小于C组,且有3只荷瘤鼠肿瘤完全消退。其余3组荷瘤鼠未见肿瘤完全消退。与A、B、D组相比,C、E组荷瘤鼠生存率显著改善(P<0．01),而C、E两组荷瘤鼠生存率差异无统计学意义(P> 0．05)。复种试验表明,C、E组荷瘤鼠再次成瘤率低于对照组,E组与C组差异也有统计学意义(P< 0．01);第3次接种后,E组成瘤率显著低于C组(P<0．01)。E组中5只首次接种未成瘤的小鼠,于第21天重复接种H22-Wt细胞,小鼠100％排斥肿瘤,于第56天第3次接种H22／Wt细胞,小鼠仍然100％排斥肿瘤。结论CD80+CD86和CD137L单独或者联合表达均可显著降低野生型H22细胞株致瘤性,CD80、CD86和CD137L基因联合表达显著改善了野生型H22细胞的免疫原性。
Objective To investigate the effect of the combined expression of CD80, CD86 and CD137L on the immunogenicity of tumor. Methods BALB / c mice were randomly divided into three groups: H22-Wt cell group, H22-neo cell group, H22-CD80 / CD86 + cell group and H22 (H22-CD80 / CD86 / CD137L + cells) and H22-BALB / c mice were established. The A and B groups served as the control group. Mice were observed for tumor formation, tumor formation latency, survival rate of tumor-bearing mice and tumor proliferation. Effects of Transgenes on Immunogenicity and Immune Protection of H22 Mutants by Multiple Cropping Test. Results The initial inoculation rate in group E was only 50.0%, significantly lower than the other 4 groups (P <0.01). After the first inoculation, tumor growth of tumor-bearing mice in group C was significantly inhibited, and the tumor of two tumor-bearing mice completely regressed. The inhibition of tumor growth in group E was more obvious than that in group C, the peak volume of tumor was significantly smaller than that in group C, and the tumor of three tumor-bearing mice completely subsided. The remaining three groups of tumor-bearing mice did not completely disappear tumor. Compared with groups A, B and D, the survival rates of tumor bearing mice in groups C and E were significantly improved (P <0.01), but there was no significant difference in the survival rates between groups C and E (P> 0.05). 05). Multiple inoculation experiments showed that the tumorigenic rate of tumor bearing mice in groups C and E was lower than that in control group, and the difference between group E and group C was also statistically significant (P <0.01). After the third inoculation, the rate of tumor formation in group E was significantly lower In group C (P <0.01). Five of the mice in Group E were naive for the first time, H22-Wt cells were inoculated on day 21, tumors were rejected 100% in mice, H22 / Wt cells were inoculated for the third time on day 56 and mice were still 100% Tumor. Conclusion CD80 + CD86 and CD137L alone or in combination can significantly reduce the tumorigenicity of wild-type H22 cell line. The co-expression of CD80, CD86 and CD137L genes significantly improved the immunogenicity of wild-type H22 cells.