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.
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)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
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)。
