摘要 目的观察脾多肽联合化疗对三阴性乳腺癌免疫功能及程序性死亡受体1(PD-1)/程序性死亡受体-配体1(PD-L1)表达的影响。方法山西省肿瘤医院2018年3月至2019年2月收治的三阴性乳腺癌改良根治患者40例,分为对照组(n=20)及干预组(n=20),对照组采用常规化疗,干预组在常规化疗的基础上加用脾多肽,观察两组治疗前后免疫相关指标及外周血PD-1/PD-L1表达的影响。免疫组织化学法检测三阴性乳腺癌患者癌组织及癌旁组织中PD-1及PD-L1蛋白的表达。体外培养三阴性乳腺癌MDA-MB-231细胞株,流式细胞术检测脾多肽作用后对细胞周期的影响,蛋白质印迹法(Western blot)检测脾多肽作用后对细胞PD-1及PD-L1蛋白表达的影响。多组计数资料比较采用方差分析,两两比较采用t检验。结果对照组化疗后T细胞总数低于化疗前(59.93±3.43比65.28±3.29,t=-4.452,P<0.05),差异均有统计学意义,干预组化疗后CD4+T细胞(41.47±3.67比34.69±3.61,t=5.783,P<0.05)及T细胞总数(69.33±3.59比63.25±3.29,t=3.686,P<0.05)高于化疗前,差异均有统计学意义。干预组化疗后外周血PD-1(5.74±0.52比4.81±0.35,t=3.325,P<0.05)/PD-L1(5.14±0.29比4.30±0.21,t=4.453,P<0.05)低于化疗前,差异均有统计学意义。PD-1(11比2,χ2=7.440,P<0.05)及PD-L1(17比4,χ2=10.912,P<0.05)在三阴性乳腺癌组织中的阳性表达率高于癌旁组织,差异均有统计学意义,PD-1在三阴性乳腺癌中的表达与患者的组织学分级有关(8比3,χ2=4.713,P<0.05),PD-L1在三阴性乳腺癌中的表达与患者的临床分期有关(11比6,χ2=5.966,P<0.05),差异均有统计学意义。脾多肽干预后,MDA-MB-231细胞G0/G1期细胞比例降低(F=5.998,P<0.05),S期比例增高(F=10.375,P<0.05),PD-1(F=32.123,P<0.05)及PD-L1(F=37.550,P<0.05)蛋白的表达显著降低,差异均有统计学意义。结论脾多肽可改善三阴性乳腺癌化疗患者的T细胞免疫功能,下调患者外周血及细胞株中PD-1/PD-L1的表� Objective To study the effects of lienal polypeptide injection combined with chemotherapy on the immune function and programmed death-1(PD-1)/programmed death ligand-1(PD-L1)expression in triple negative breast cancer.Methods From March 2018 to February 2019,a total of 40 patients with triple negative breast cancer undergoing modified radical mastectomy in Shanxi Cancer Hospital were divided into the control group(n=20)and the intervention group(n=20).The control group and intervention group received conventional chemotherapy.The intervention group was given lienal polypeptide injection additionally.The immune related indicators and PD-1/PD-L1 in peripheral blood were detected before and after treatment by flow cytometry.Immunohistochemistry was used to detect the expression of PD-1 and PD-L1 protein in cancer tissues and paracancerous tissues of patients with triple negative breast cancer.The triple negative breast cancer MDA-MB-231 cell line was cultured in vitro.The effect of lienal polypeptide injection on cell cycle was detected by flow cytometry.The effect of lienal polypeptide injection on the expression of PD-1 and PD-L1 protein was detected by Western blotting.Results The total number of T cells in the control group decreased significantly after chemotherapy(59.93±3.43 vs.65.28±3.29,t=-4.452,P<0.05).The total number of CD4+T cells(41.47±3.67 vs.34.69±3.61,t=5.783,P<0.05)and T cells(69.33±3.59 vs.63.25±3.29,t=3.686,P<0.05)in the intervention group increased significantly.Peripheral blood PD-1(5.74±0.52 vs.4.81±0.35,t=3.325,P<0.05)PD-L1(5.14±0.29 vs.4.30±0.21,t=4.453,P<0.05)in the intervention group were significantly lower than that before chemotherapy.The positive expression rate of PD-1(11 vs.2,χ2=7.440,P<0.05)and PD-L1(17 vs.4,χ2=10.912,P<0.05)in triple-negative breast cancer tissues was significantly increased,and the expression of PD-1 in triple-negative breast cancer was correlated with histological grade(8 vs.3,χ2=4.713,P<0.05).The expression of PD-L1 in triple-negative breast
出处 《中华实验外科杂志》 CAS 北大核心 2021年第4期610-614,共5页 Chinese Journal of Experimental Surgery
基金 山西省回国留学人员科研资助项目(2020-176)。
分类号 R73 [医药卫生—肿瘤]
