基于PD-1/PD-L1通路探讨补肾解毒散结方对晚期结直肠癌患者免疫微环境的影响

Effect of Bushen Jiedu Sanjie Recipe on immune micro-environment of patients with advanced colorectal cancer based on PD-1/PD-L1 pathway

目的分析基于细胞程序性死亡受体1(Programmed death receptor-1,PD-1)/细胞程序性死亡受体-配体1(Programmed death receptor ligand-1,PD-L1)通路探讨补肾解毒散结方对晚期结直肠癌患者免疫微环境的影响。方法选择2020年1月-2021年12月上海中医药大学附属曙光医院胃肠外科收治的50例晚期结直肠癌患者,按照随机数字表法分为研究组和对照组。对照组(n=25)采用mFOLFOX6化疗+PD-1抑制剂,研究组(n=25)在此基础上给予补肾解毒散结方,服用2周。分别于治疗前、治疗后(化疗4个周期),采用流式细胞仪检测T淋巴细胞亚群,酶联免疫吸附法检测血清PD-1、PD-L1水平,分析其表达与临床疗效及免疫微环境的关系。结果研究组的疾病控制率(Disease control rate,DCR)为64.0%,明显高于对照组36.0%(P<0.05);治疗后,研究组CD3^(+)、CD4^(+)水平明显升高(P<0.05),CD8^(+)、CD4^(+)/CD8^(+)较治疗前差异无统计学意义(P>0.05),研究组T细胞亚群各指标均较对照组显著改善(P<0.05);治疗后,两组体液免疫指标均明显升高(P<0.05),研究组IgA、IgM水平均高于对照组(P<0.05)。研究组治疗后外周血PD-1、PD-L1水平明显降低,且低于对照组(P<0.05);研究组患者中,有效组外周血CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)及IgA、IgG、IgM水平明显升高,PD-1、PD-L1水平明显降低(P<0.05)。结论补肾解毒散结方可调节晚期结直肠癌患者的免疫微环境,改善临床疗效,其作用机制可能与抑制PD-1/PD-L1信号通路相关。

Objective To investigate the effect of Bushen Jiedu Sanjie Recipe on immune micro-environment of patients with advanced colorectal cancer based on programmed death molecule 1/programmed death-ligand 1(PD-1/PD-L1)pathway.Methods Fifty patients with advanced colorectal cancer admitted to the Department of Gastrointestinal surgery,Shuguang Hospital,Shanghai University of Traditional Chinese Medicine from January 2020 to December 2021 were selected and divided into research group and control group according to random number table method.The control group(n=25)was given mFOLFOX6 chemotherapy+PD-1 inhibitor,and the research group(n=25)was given Bushen Jiedu Sanjie Recipe for 2 weeks on the basis of the treatment for control group.Before and after treatment(4 cycles of chemotherapy),T lymphocyte subsets were detected by flow cytometry,serum PD-1 and PD-L1 levels were detected by enzyme-linked immunosorbent assay,and the relationship between their expression and clinical efficacy and immune micro-environment was analyzed.Results The DCR(disease control rate)of research group was 64.0%,which was significantly higher than that of control group(36.0%)(P<0.05).After treatment,the levels of CD3^(+)and CD4^(+)in research group were significantly increased(P<0.05),while the levels of CD8^(+)and CD4^(+)/CD8^(+)had no significant difference compared with those before treatment(P>0.05).The indexes of T cell subsets in research group were significantly higher than those in control group(P<0.05).After treatment,the humoral immune indexes of the two groups were significantly increased(P<0.05),and the levels of IgA and IgM in research group were higher than those in control group(P<0.05).After treatment,the levels of PD-1 and PD-L1 in peripheral blood of research group were decreased,and were significantly lower than those of control group(P<0.05).In the research group,the levels of CD3^(+),CD4^(+),CD8^(+)and CD4^(+)/CD8^(+)and IgA,IgG,IgM in peripheral blood of the effective group were significantly increased,while the levels of PD-1 and PD-L1 were significantly decreased(P<0.05).Conclusion Bushen Jiedu Sanjie Recipe can regulate the immune micro-environment of patients with advanced colorectal cancer and improve clinical efficacy.Its mechanism may be related to the inhibition of PD-1/PD-L1 signaling pathway.