^(125)I粒子植入联合抗PD-1治疗对小鼠Lewis肺癌的抑制作用研究

Effect of iodine-125 particle implantation combined with anti-PD-1 therapy on Lewis lung cancer in mice

目的:研究^(125)I粒子植入对免疫微环境的影响,以及^(125)I粒子植入联合抗程序性死亡受体-1(programmed cell death receptor-1,PD-1)治疗的抗肿瘤疗效。方法:在小鼠右后肢皮下注射Lewis肺癌(LLC)细胞构建肿瘤模型,利用流式细胞术分析^(125)I粒子植入后PD-1、程序性死亡配体1(programmed death-ligand 1,PD-L1)、Treg细胞的表达。在小鼠右后肢(原位肿瘤)和左前肢(远位肿瘤)皮下注射LLC细胞,将小鼠随机分为PBS组、抗PD-1组、^(125)I粒子植入组和联合治疗组。绘制肿瘤生长曲线,流式分析肿瘤浸润CD4^(+)及CD8^(+)T细胞比例。结果:^(125)I粒子植入12天后PD-L1及PD-1表达上调(P<0.01),Treg表达无显著性差异(P=0.196)。与其余各组相比,联合治疗组小鼠原位和远位肿瘤生长均受到明显抑制(均P<0.05),肿瘤浸润CD8^(+)T细胞比例显著增加(均P<0.05)。结论:^(125)I粒子植入联合抗PD-1治疗能激活机体抗肿瘤免疫,协同抑制小鼠LLC生长。

Objective:To study the effect of iodine-125 particle implantation(^(125)I RPI)on the immune microenvironment and to determine the antitumor efficacy of^(125)I particles combined with anti-programmed cell death receptor 1(PD-1)therapy.Methods:Lewis lung cancer(LLC)cells were subcutaneously injected in mice to establish LLC mouse models.The expression of PD-1,PD-L1,and Treg cells was determined through flow cytometry following^(125)I RPI in these mice.LLC cells were subcutaneously injected into the right hind limb(primary tumor)and left flank(secondary tumor)of mice,and the mice were randomly assigned into PBS,anti-PD-1,^(125)I RPI,and combination therapy groups.The volumes of the primary and secondary tumors were measured,tumor growth curve was generated,and proportions of CD4+and CD8+T cells in the tumor tissue were analyzed via flow cytometry.Results:The expression of PD-1 and PD-L1 was significantly upregulated on day 12 after^(125)I RPI(P<0.01);however,there was no significant difference in Treg expression(P=0.196).The growth of primary and secondary tumors was significantly inhibited(P<0.05)and proportion of CD8+T cells was significantly increased(P<0.05)in the combination therapy group compared to the other groups.Conclusions:^(125)I RPI combined with anti-PD-1 therapy can activate anti-tumor immunity and inhibit the growth of LLC in mice.