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图1 使用检查点抑制剂治疗的患者在COVID-19活跃期表现出典型的转录组和蛋白质组炎症反应
(A至C)来自一组非黑色素瘤患者和一组接受PD-1治疗患者的COVID-19活跃期患者和健康对照的全血转录组谱。(A)抗PD-1治疗队列中covid -19感染患者和未感染患者之间100个差异最大的基因热图。(B) PD-1治疗队列中COVID-19活跃期富集通路的GSEA。(C)每个队列中COVID-19患者与未感染患者之间RNA表达倍数的变化。每个点代表一个基因。(D)来自两个队列患者的RNA表达数据,每个队列归一化为未感染组的平均值。(E)两组患者的蛋白质组数据,归一化如(D)所示。每个点对应一个患者,柱状图代表平均值。使用未配对t检验确定显著性。*P < 0.05, **P < 0.01。MHC,主要组织相容性复合体;TLR, toll样受体;NLR, nod样受体。
图2 接受ICI治疗的患者显示T细胞活化谱升高
(A)去除粒细胞后的血白细胞viSNE图,用30个标记物染色,用海量细胞仪测量。细胞根据它们表达的标记的组合(左)自动分离成空间上不同的子集。LTγδ, γδ T淋巴细胞;MAIT,粘膜相关不变T细胞;LB、B淋巴细胞;NK,自然杀伤细胞。然后根据两组感染和未感染患者的细胞密度对viSNE图进行着色。红色表示细胞密度最高,蓝色表示细胞密度最低。(B)外周血淋巴细胞中CD3+ T细胞、CD19+ B细胞、CD3−CD56+ NK细胞、MAIT细胞的比例。(C和D) T细胞亚群的比例。(E)根据活化(CD38和HLA-DR)、衰竭(PD-1)和Tfh标记(CXCR5+PD-1+)的表达分析特定T细胞亚群的功能状态。(F) B细胞亚群比例。(G)用S- flow法定量SARS-CoV-2 spike (S)特异性IgG抗体。左:表达S蛋白的细胞百分比。右:归一化平均荧光强度(MFI)每个点对应一个病人,条形图代表平均值。采用未配对t检验,然后进行多重检验的Holm-Sidak校正来确定显著性。*P < 0.05, **P < 0.01, ***P < 0.001。
图3 ICI治疗对SARS-CoV-2抗病毒细胞免疫具有持久影响。
(A)采集COVID-19恢复期患者全血,用刺突蛋白(S)、核蛋白(NP)或膜蛋白(M)肽池刺激48小时,然后收集上清,采用数字ELISA法检测IFN-γ。刺激指数由每个队列的未感染组归一化的IFN-γ浓度组成。(B)恢复期患者淋巴细胞的Fit-SNE图,用海量细胞仪测量,图按细胞密度着色。红色表示细胞密度最高,蓝色表示细胞密度最低。(C)两组恢复期患者T细胞亚群的比例。(D)每种Ig亚型SARS-CoV-2 s特异性IgG+、IgA+或IgM+细胞的频率。(E) ICI治疗患者SARS-CoV-2 s特异性IgG+的寿命,以百分比或MFI表示。每个点对应一个样本(n = 33),柱状表示平均值。采用局部估计散点平滑法得到非参数回归曲线。使用未配对t检验确定显著性。*P < 0.05, **P < 0.01, ***P < 0.001。IC50,中值抑制浓度。
本文仅作信息分享,不代表礼进生物公司立场和观点,也不作治疗方案推荐和介绍。如有需求,请咨询和联系正规医疗机构。
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