摘要
目的:探讨抗PD-1抗体对小鼠结直肠癌移植瘤组织中免疫细胞的影响。方法:构建BALB/c小鼠CT26结直肠癌模型,随机分为抗PD-1抗体治疗组(PD-1组)和对照组(PBS组)。PD-1组在荷瘤后第6天和第9天分别腹腔注射抗PD-1抗体(0.2 mg/只),对照组给予相同体积的PBS。荷瘤后第7天开始采用游标卡尺每隔1 d对肿瘤进行测量、记录,计算肿瘤体积。末次给药后2周根据治疗效果和肿瘤体积大小将PD-1组小鼠分为有效组(n=3)和无效组(n=5),取其脾脏和肿瘤组织,流式法检测脾脏与肿瘤微环境中T细胞(CD3、CD4、CD8)、髓源性抑制细胞(MDSC)、调节T细胞(Tregs)等细胞比例及肿瘤细胞中PD-L1的表达。结果:治疗有效组小鼠肿瘤体积小于治疗无效组;治疗有效组小鼠脾脏和肿瘤组织中CD3^+、CD4^+和CD8^+T细胞占总细胞的比例均高于无效组,MDSC细胞的比例均低于无效组(P<0.05)。治疗有效组小鼠肿瘤组织中PD-L1的表达高于无效组(P<0.05)。抗PD-1抗体治疗后肿瘤组织中PD-L1的表达与肿瘤组织中浸润的CD3^+、CD4^+和CD8^+T细胞的比例均呈正相关(P<0.05)。结论:小鼠CT26结直肠癌模型中抗PD-1抗体的治疗效果与肿瘤组织中浸润T细胞和MDSC比例的改变密切相关,其可能成为预测和改善抗PD-1抗体治疗效果的检测指标。
Aim:To investigate the effects of anti-PD-1 antibody on the immune cell ratio of mice with colorectal cancer.Methods:BALB/c mice were inoculated subcutaneously with CT26 at day0.After 6 days,mice were randomized into PD-1 group(treated with anti-PD-1 antibody,0.2 mg/mouse)and PBS group(treated with same volume PBS)by intraperitoneal injection two times(day6 and day9).On the 7th day after tumor bearing,vernier calipers were used to measure the tumor volume every 2 days.Two weeks after the last treatment,the mice were sacrificed and divided into anti-PD-1 antibody response group(n=3)and no-response group(n=5)according to tumor volume,the spleen and tumor tissues were taken,the ratio of CD3,CD4,CD8,myeloid-derived suppressor cells(MDSC),and Tregs as well as the expression of PD-L1 on tumor cells were detected by flow cytometry.Results:The tumor volume of the response group was significantly smaller than that of the no-response group.The proportion of CD3^+,CD4^+and CD8^+T cells among the total cells in spleen and tumor tissues of the response group was all significantly higher than that in the no-response group,and the proportion of MDSC among the CD45 positive cells in spleen and tumor tissues of the response group was significantly lower than that in no-response group(P<0.05).The expression of PD-L1 on tumor cells in the response group was significantly higher than that in no-response group(P<0.05).The expression of PD-L1 in tumor tissue as positively correlated with the proportion of CD3^+,CD4^+and CD8^+T cells in tumor tissue in the response group(P<0.05).Conclusion:The therapeutic effect of anti-PD-1 antibody in mouse CT26 model is closely related to the change of the proportion of tumor infiltrating T cells and MDSC in tumor tissues,which may be an indicator to predict and improve the therapeutic effect of anti-PD-1 antibody.
作者
徐本玲
陈广玉
袁龙
杜雪相
高全立
XU Benling;CHEN Guangyu;YUAN Long;DU Xuexiang;GAO Quanli(Department of Cancer Immunotherapy,the Affiliated Cancer Hospital,Zhengzhou University,Zhengzhou 450008;Henan Engineering Laboratory of Immunotherapy for Malignant Tumor,Zhengzhou 450008;Department of General Surgery,the Affiliated Cancer Hospital,Zhengzhou University,Zhengzhou 450008)
出处
《郑州大学学报（医学版）》
CAS
北大核心
2020年第1期33-36,共4页
Journal of Zhengzhou University(Medical Sciences)
基金
国家自然科学基金项目(81502468)
河南省科技厅科技攻关项目(182102310387,162300410095)
