PD-1 suppresses human CD38+ circulating Tfr cells and regulates humoral immunity.

IF 10.3 1区 医学 Q1 IMMUNOLOGY
Heng Zhang, Hui Zheng, Yanchun Wang, Cuncun Chen, Ying Tong, Suhong Xie, Xiaolu Ma, Lin Guo, Renquan Lu
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引用次数: 0

Abstract

Background: Anti-programmed cell death protein 1 (anti-PD-1) antibodies have achieved revolutionary success in cancer therapy. However, the impact of anti-PD-1 therapy on host humoral immunity in humans during cancer immunotherapy requires further investigation.

Methods: We evaluated immunoglobulin titers by ELISA and screened the immune landscape of immune cells from 25 healthy donors and 50 cases including 25 new-onset hepatocellular carcinoma (HCC) patients prior to systemic treatment and 25 HCC patients undergoing anti-PD-1 therapy by multicolor flow cytometry. Flow or beads sorted cells were cultured ex vivo for proliferation and functional analysis.

Results: Anti-PD-1 therapy significantly increased the levels of IgG and IgA in the periphery of HCC patients. Anti-PD-1 treatment led to an increase in plasmablasts and a notable rise in circulating T follicular regulatory (cTfr) cells, while changes in circulating B cells, T follicular helper cells, or regulatory T cells were not significant. Anti-PD-1 therapy also influenced the proliferation and function of cTfr cells, promoting the differentiation of CD38+ cTfr cells. We observed that the CD38+ Tfr cell subset in the peripheral blood can promote plasmablast differentiation, associated with altered antibody production.

Conclusions: Together, these data demonstrate the immunomodulatory role of PD-1 in restricting the differentiation and function of human cTfr cells and in regulating humoral immunity.

PD-1 抑制人类 CD38+ 循环 Tfr 细胞并调节体液免疫。
背景:抗程序性细胞死亡蛋白1 (anti-PD-1)抗体在癌症治疗中取得了革命性的成功。然而,在癌症免疫治疗过程中,抗pd -1治疗对人体宿主体液免疫的影响还有待进一步研究。方法:采用ELISA法检测免疫球蛋白滴度,采用多色流式细胞术对25例健康供体和50例肝细胞癌患者(包括25例接受全身治疗前的新发肝细胞癌患者和25例接受抗pd -1治疗的肝细胞癌患者)免疫细胞的免疫景观进行筛选。流式或珠状分选细胞体外培养进行增殖和功能分析。结果:抗pd -1治疗可显著提高HCC患者外周血IgG和IgA水平。抗pd -1治疗导致浆母细胞增加,循环T滤泡调节细胞(cTfr)显著增加,而循环B细胞、T滤泡辅助细胞或调节性T细胞的变化不显著。抗pd -1治疗还能影响cTfr细胞的增殖和功能,促进CD38+ cTfr细胞的分化。我们观察到外周血中的CD38+ Tfr细胞亚群可以促进浆母细胞分化,并与改变的抗体产生相关。结论:这些数据表明PD-1在限制人cTfr细胞的分化和功能以及调节体液免疫方面具有免疫调节作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal for Immunotherapy of Cancer
Journal for Immunotherapy of Cancer Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
17.70
自引率
4.60%
发文量
522
审稿时长
18 weeks
期刊介绍: The Journal for ImmunoTherapy of Cancer (JITC) is a peer-reviewed publication that promotes scientific exchange and deepens knowledge in the constantly evolving fields of tumor immunology and cancer immunotherapy. With an open access format, JITC encourages widespread access to its findings. The journal covers a wide range of topics, spanning from basic science to translational and clinical research. Key areas of interest include tumor-host interactions, the intricate tumor microenvironment, animal models, the identification of predictive and prognostic immune biomarkers, groundbreaking pharmaceutical and cellular therapies, innovative vaccines, combination immune-based treatments, and the study of immune-related toxicity.
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