B7/CD28家族分子作为主要的共信号分子,在T细胞功能调控及免疫应答中发挥着至关重要的作用,关于其功能的研究及应用在世界范围内广泛开展。其中,CD28和CTLA-4都可以与B7-1/B7-2结合,但CD28能够促进T细胞增殖,维持Treg细胞稳态;而CTLA-4...B7/CD28家族分子作为主要的共信号分子,在T细胞功能调控及免疫应答中发挥着至关重要的作用,关于其功能的研究及应用在世界范围内广泛开展。其中,CD28和CTLA-4都可以与B7-1/B7-2结合,但CD28能够促进T细胞增殖,维持Treg细胞稳态;而CTLA-4则可以抑制T细胞增殖,影响CD4;T细胞的分化;抗CTLA-4单抗ipilimumab与抗PD-1单抗联用能够用于治疗PD-L1;的非小细胞肺癌以及无症状的Ⅳ期黑色素瘤。PD-L1/PD-L2:PD-1途径则可以通过多种方式调节T细胞功能,参与CD8;T细胞"耗竭"状态的形成与维持。目前,针对PD-L1/PD-L2:PD-1途径的免疫治疗相关药物开发广泛且较为成熟,抗PD-1单抗主要通过诱导肿瘤浸润的部分耗竭的CD8;T细胞亚群的扩增发挥抗肿瘤作用。ICOS:ICOSL途径在T细胞分化、细胞因子分泌以及体液免疫应答中起着重要作用,抗ICOS抗体药物feladilimab与抗PD-1单抗联用能够有效治疗多发性或难治性骨髓瘤。B7-H3同时具有共刺激效应和共抑制效应,阻断B7-H3后能够有效增强TIL的抗肿瘤效应,其单抗enoblituzumab能够与抗PD-1单抗联用治疗非小细胞肺癌。B7-H4、人内源性逆转录病毒-H长末端重复关联蛋白(human endogenous retrovirus-H long terminal repeat-associating protein,HHLA)以及含V结构域抑制T细胞活化的免疫球蛋白(V-domain Ig-cotaining suppressor of T cell activation,VISTA)均能够提供抑制信号,针对B7-H4靶点的CAR-T治疗以及VISTA的小分子抑制剂CA-170均有临床试验正在进行中。目前,对共信号分子的研究已经获得了长足进展,针对某些活化性分子或者抑制性分子开发了相关抗肿瘤药物并在临床中取得一定成效,但如何进一步提高其治疗有效率、减少不良反应等仍有待探索。展开更多
Objective: To study the correlation of peripheral blood COS, OX40 and CD40 expression with disease activity in patients with lupus nephritis (LN). Methods: Patients who were diagnosed with stable and active lupus neph...Objective: To study the correlation of peripheral blood COS, OX40 and CD40 expression with disease activity in patients with lupus nephritis (LN). Methods: Patients who were diagnosed with stable and active lupus nephritis in Zigong First People's Hospital between May 2014 and March 2017 were selected and enrolled in stable LN group and active LN group respectively;healthy volunteers who received physical examination during the same period were chosen as control group. The ICOS, OX40 and CD40 mRNA expression in peripheral blood nuclear cells as well as the levels of cytokines and disease activity-related indexes in serum were measured. Results: ICOS, OX40 and CD40 mRNA expression in peripheral blood mononuclear cells as well as IL-4, IL-5, IL-10, anti-C1q antibody and anti-ds-DNA antibody levels in serum of stable LN group and active LN group were significantly higher than those of control group while TNF-α, IFN-γ, C3 and C4 levels in serum were significantly lower than those of control group;the changes in active LN group were more significant than those in stable LN group;ICOS, OX40 and CD40 mRNA expression in peripheral blood mononuclear cells of patients with LN were positively correlated with IL-4, IL-5, IL-10, anti-C1q antibody and anti-ds-DNA antibody levels in serum, and negatively correlated with TNF-α, IFN-γ, C3 and C4 levels in serum. Conclusion: High expression of ICOS, OX40 and CD40 in the peripheral blood of patients with LN are closely related to the Th1/Th2 shifting and the disease activity.展开更多
文摘B7/CD28家族分子作为主要的共信号分子,在T细胞功能调控及免疫应答中发挥着至关重要的作用,关于其功能的研究及应用在世界范围内广泛开展。其中,CD28和CTLA-4都可以与B7-1/B7-2结合,但CD28能够促进T细胞增殖,维持Treg细胞稳态;而CTLA-4则可以抑制T细胞增殖,影响CD4;T细胞的分化;抗CTLA-4单抗ipilimumab与抗PD-1单抗联用能够用于治疗PD-L1;的非小细胞肺癌以及无症状的Ⅳ期黑色素瘤。PD-L1/PD-L2:PD-1途径则可以通过多种方式调节T细胞功能,参与CD8;T细胞"耗竭"状态的形成与维持。目前,针对PD-L1/PD-L2:PD-1途径的免疫治疗相关药物开发广泛且较为成熟,抗PD-1单抗主要通过诱导肿瘤浸润的部分耗竭的CD8;T细胞亚群的扩增发挥抗肿瘤作用。ICOS:ICOSL途径在T细胞分化、细胞因子分泌以及体液免疫应答中起着重要作用,抗ICOS抗体药物feladilimab与抗PD-1单抗联用能够有效治疗多发性或难治性骨髓瘤。B7-H3同时具有共刺激效应和共抑制效应,阻断B7-H3后能够有效增强TIL的抗肿瘤效应,其单抗enoblituzumab能够与抗PD-1单抗联用治疗非小细胞肺癌。B7-H4、人内源性逆转录病毒-H长末端重复关联蛋白(human endogenous retrovirus-H long terminal repeat-associating protein,HHLA)以及含V结构域抑制T细胞活化的免疫球蛋白(V-domain Ig-cotaining suppressor of T cell activation,VISTA)均能够提供抑制信号,针对B7-H4靶点的CAR-T治疗以及VISTA的小分子抑制剂CA-170均有临床试验正在进行中。目前,对共信号分子的研究已经获得了长足进展,针对某些活化性分子或者抑制性分子开发了相关抗肿瘤药物并在临床中取得一定成效,但如何进一步提高其治疗有效率、减少不良反应等仍有待探索。
文摘Objective: To study the correlation of peripheral blood COS, OX40 and CD40 expression with disease activity in patients with lupus nephritis (LN). Methods: Patients who were diagnosed with stable and active lupus nephritis in Zigong First People's Hospital between May 2014 and March 2017 were selected and enrolled in stable LN group and active LN group respectively;healthy volunteers who received physical examination during the same period were chosen as control group. The ICOS, OX40 and CD40 mRNA expression in peripheral blood nuclear cells as well as the levels of cytokines and disease activity-related indexes in serum were measured. Results: ICOS, OX40 and CD40 mRNA expression in peripheral blood mononuclear cells as well as IL-4, IL-5, IL-10, anti-C1q antibody and anti-ds-DNA antibody levels in serum of stable LN group and active LN group were significantly higher than those of control group while TNF-α, IFN-γ, C3 and C4 levels in serum were significantly lower than those of control group;the changes in active LN group were more significant than those in stable LN group;ICOS, OX40 and CD40 mRNA expression in peripheral blood mononuclear cells of patients with LN were positively correlated with IL-4, IL-5, IL-10, anti-C1q antibody and anti-ds-DNA antibody levels in serum, and negatively correlated with TNF-α, IFN-γ, C3 and C4 levels in serum. Conclusion: High expression of ICOS, OX40 and CD40 in the peripheral blood of patients with LN are closely related to the Th1/Th2 shifting and the disease activity.
