STING激动剂联合PD-1抗体通过激活T细胞的抗肿瘤活性抑制肺癌进展的研究  

STING agonist combined with PD-1 antibody inhibits lung cancer progression by activating antitumor activity of T cells

作　　者：张西科 杨建彬 邵鸿飞 康利娜 刘艳玲 刘杰 ZHANG Xike;YANG Jianbin;SHAO Hongfei;KANG Lina;LIU Yanling;LIU Jie(Department of Pharmacy,Xingtai People's Hospital,Affiliated Hospital of Hebei Medical University,Xingtai 054000,China)

机构地区：[1]邢台市人民医院,河北医科大学附属医院药剂科,邢台054000 [2]河北医科大学基础医学院药理学教研室,石家庄050017

出　　处：《中国免疫学杂志》2023年第7期1469-1473,共5页Chinese Journal of Immunology

基　　金：河北省医学科学项目研究课题计划项目(20200119)。

摘　　要：目的:探索STING激动剂联合PD-1抗体是否可以有效激活体内的T细胞,发挥抑制肺癌进展的作用。方法:通过CFSE检测T细胞的体外增殖情况;通过ELISA法检测T细胞的细胞因子分泌能力;利用小鼠皮下移植瘤模型验证STING激动剂联合PD-1抗体对肿瘤细胞的体内抑制作用;利用免疫荧光实验检测CD3+T细胞的肿瘤浸润情况;通过流式细胞术检测肿瘤浸润T细胞IFN-γ分泌情况;利用免疫组化法检测肿瘤组织中PD-1的表达水平。结果:STING激动剂可以在体外显著增强T细胞的增殖能力(P<0.0001)以及分泌IL-2(P<0.01)和IFN-γ(P<0.01)的能力;STING激动剂联合PD-1抗体显著抑制路易斯肺癌细胞LLC在小鼠体内的生长(P<0.0001);STING激动剂联合PD-1抗体可以显著增强肿瘤组织中CD3+T细胞的浸润情况(P<0.0001),增加肿瘤组织中IFN-γ阳性的T细胞比例(P<0.0001),同时还可以显著降低肿瘤组织中PD-1的表达水平(P<0.0001)。结论:STING激动剂联合PD-1抗体可以有效激活体内T细胞的抗肿瘤免疫应答,抑制肺癌荷瘤小鼠模型的肿瘤进展,该研究对在肺癌的临床治疗中实践这一联合疗法具有重要意义。Objective:To explore whether STING agonist combined with PD-1 antibody can effectively activate T cells in vivo and play a role in inhibiting the progression of lung cancer.Methods:The proliferation of T cells in vitro was detected by CFSE.The cytokine secretion ability of T cells was detected by ELISA.The anti-tumor effect of STING agonist combined with PD-1 antibody on tu-mor cells in vivo was verified by subcutaneous transplanted tumor model in mice.The tumor invasion of CD3+T cells was detected by immunofluorescence assay.IFN-γtumor infiltrating T cells was detected by flow cytometry.Immunohistochemistry was used to detect the expression level of PD-1 in tumor tissues.Results:STING agonists could significantly enhance T cell proliferation(P<0.0001)and secretion of IL-2(P<0.01)and IFN-γ(P<0.01)in vitro.STING agonist combined with PD-1 antibody significantly inhibited the growth of Lewis lung cancer cell in mice(P<0.0001).STING agonist combined with PD-1 antibody could significantly enhance the infiltration of CD3+T cells in tumor tissues(P<0.0001),increase the proportion of IFN-γpositive T cells in tumor tissues(P<0.0001),and also significantly reduce the expression level of PD-1 in tumor tissues(P<0.0001).Conclusion:STING agonist combined with PD-1 antibody can effectively activate the anti-tumor immune response of T cells in vivo and inhibit tumor progression in lung cancer bearing mouse model.This study is of great significance for the clinical practice of this combination therapy in lung cancer.

关 键 词：肺癌 STING PD-1 T细胞 免疫治疗 

分 类 号：R734.2[医药卫生—肿瘤]