离体
免疫系统
HBcAg
免疫学
医学
外周血单个核细胞
干扰素
HBeAg
封锁
体内
免疫疗法
T细胞
乙型肝炎病毒
生物
乙型肝炎表面抗原
体外
内科学
病毒
受体
生物化学
生物技术
作者
Conan Chua,Loghman Salimzadeh,Ann T.,Oyedele Adeyi,Hobin Seo,Giselle M. Boukhaled,Aman Mehrotra,Anjali Patel,Sara Ferrando‐Martínez,Scott H. Robbins,Danie La,David Wong,Harry L.A. Janssen,David G. Brooks,Jordan J. Feld,Adam J. Gehring
标识
DOI:10.1097/hc9.0000000000000337
摘要
Background: There are no immunological biomarkers that predict control of chronic hepatitis B (CHB). The lack of immune biomarkers raises concerns for therapies targeting PD-1/PD-L1 because they have the potential for immune-related adverse events. Defining specific immune functions associated with control of HBV replication could identify patients likely to respond to anti-PD-1/PD-L1 therapies and achieve a durable functional cure. Methods: We enrolled immunotolerant, HBeAg+ immune-active (IA+), HBeAg− immune-active (IA−), inactive carriers, and functionally cured patients to test ex vivo PD-1 blockade on HBV-specific T cell functionality. Peripheral blood mononuclear cells were stimulated with overlapping peptides covering HBV proteins +/−α-PD-1 blockade. Functional T cells were measured using a 2-color FluoroSpot assay for interferon-γ and IL-2. Ex vivo functional restoration was compared to the interferon response capacity assay, which predicts overall survival in cancer patients receiving checkpoint inhibitors. Results: Ex vivo interferon-γ+ responses did not differ across clinical phases. IL-2+ responses were significantly higher in patients with better viral control and preferentially restored with PD-1 blockade. Inactive carrier patients displayed the greatest increase in IL-2 production, which was dominated by CD4 T cell and response to the HBcAg. The interferon response capacity assay significantly correlated with the degree of HBV-specific T cell restoration. Conclusions: IL-2 production was associated with better HBV control and superior to interferon-γ as a marker of T cell restoration following ex vivo PD-1 blockade. Our study suggests that responsiveness to ex vivo PD-1 blockade, or the interferon response capacity assay, may support stratification for α-PD-1 therapies.
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