军事医学2024，Vol.48Issue(4)：273-280,8.DOI:10.7644/j.issn.1674-9960.2024.04.005
安罗替尼联合抗PD-1抗体重塑小鼠结肠癌模型免疫微环境的机制研究
Mechanisms of anlotinib combined with anti-PD1 antibody for remodeling the immune microenvironment of a colon cancer mouse model
摘要
Abstract
Objective To investigate the inhibitory effect of anlotinib combined with anti-PD1 antibody on a colon cancer mouse model,and to explore its possible mechanismfor remodeling the immune system and tumor microenvironment.Methods A BALB/c mouse model was established with colon cancer cells CT26,and the mice were divided randomly into four groups:the control group,the anlotinib group,anti-PD1 antibody group and anlotinib combined with anti-PD1 antibody group,with 6 mice in each.During the experiment,tumor volumes were measured every 2 days using a vernier caliper.After the experiment(on day 14),the weight of the tumors of mice in each group was measured.Flow cytometry was used to detect changes in the number of immune infiltrating cells in tumor tissues,including CD4+T cells,CD8+T cells,monocytic myeloid-derived suppressor cells(M-MDSCs),granulocytic myeloid-derived suppressor cells(G-MDSCs),and M2-type tumor-associated macrophages(M2-TAM).Furthermore,ELISA was employed to detect the levels of vascular endothelial growth factor(VEGF),interferon-γ(IFN-γ),interleukin-17(IL-17),and IL-10 in the serum of mice.Results Compared with the control group,the other three groups showed a decrease in the volume and weight of transplanted tumors in mice(P＜0.05),as well as decreased levels of cytokines VEGF,IL-10(P＜0.05),and IL-17(P＜0.01).Additionally,there was an increase in the level of IFN-γ(P＜0.05).In terms of the number of immune infiltrating cells,the number of M-MDSCs decreased in each treatment group compared to the control group,but without statistically significant difference(P＞0.05).In the combined group,the number of M2-type TAMs decreased compared to the control group and the anti-PD-1 antibody group(P＜0.05).Furthermore,flow cytometry results indicated that compared to the control group,the other three groups showed an increase in the number of CD8+T cells in mice(P＜0.05).The number of CD4+T cells decreased slightly compared to the other groups,but the statistically significant difference was only observed when compared to the anlotinib group(P＜0.05).Conclusion The combination ofanlotinib and anti-PD1 antibody may regulate the levels of cytokines VEGF,IFN-γ,IL-10,and IL-17,thereby influencing the number of immunosuppressive cells in the tumor microenvironment.The tumor microenvironment and immunity can also be improved,thus significantly inhibiting the growth ofmouse colonic transplant tumors.关键词
结肠肿瘤/小鼠模型/安罗替尼/抗PD-1抗体/肿瘤微环境/免疫机制Key words
colon cancer/mouse model/anlotinib/anti-PD1 antibody/tumour microenvironment/immune mechanism分类
医药卫生引用本文复制引用
马军朋,温居一,杜鹏,赵向飞..安罗替尼联合抗PD-1抗体重塑小鼠结肠癌模型免疫微环境的机制研究[J].军事医学,2024,48(4):273-280,8.基金项目
"十三五"国家重点研发计划(2017YFC0112102,2017YFC0112104) （2017YFC0112102,2017YFC0112104）
