Restoration of HBV-specific CD8+ T-cell responses by sequential low-dose IL-2 treatment in non-responder patients after IFN-α therapy
Abstract Patients with chronic hepatitis B (CHB) undergoing interferon (IFN)-α-based therapies often exhibit a poor HBeAg serological response. Thus, there is an unmet need for new therapies aimed at CHB. This study comprised two clinical trials, including 130 CHB patients, who were treatment-naïve;...
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2021
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oai:doaj.org-article:21b417eb6d294715b19d0a664f3c43a82021-11-07T12:14:19ZRestoration of HBV-specific CD8+ T-cell responses by sequential low-dose IL-2 treatment in non-responder patients after IFN-α therapy10.1038/s41392-021-00776-02059-3635https://doaj.org/article/21b417eb6d294715b19d0a664f3c43a82021-11-01T00:00:00Zhttps://doi.org/10.1038/s41392-021-00776-0https://doaj.org/toc/2059-3635Abstract Patients with chronic hepatitis B (CHB) undergoing interferon (IFN)-α-based therapies often exhibit a poor HBeAg serological response. Thus, there is an unmet need for new therapies aimed at CHB. This study comprised two clinical trials, including 130 CHB patients, who were treatment-naïve; in the first, 92 patients were systematically analyzed ex vivo for interleukin-2 receptor (IL-2R) expression and inhibitory molecules expression after receiving Peg-IFN-α-2b therapy. In our second clinical trial, 38 non-responder patients, in whom IFN-α therapy had failed, were treated with or without low-dose IL-2 for 24 weeks. We then examined the hepatitis B virus (HBV)-specific CD8+ T-cell response and the clinical outcome, in these patients. Although the majority of the participants undergoing Peg-IFN-α-2b therapy were non-responders, we observed a decrease in CD25 expression on their CD4+ T cells, suggesting that IFN-α therapy may provide a rationale for sequential IL-2 treatment without increasing regulatory T cells (Tregs). Following sequential therapy with IL-2, we demonstrated that the non-responders experienced a decrease in the numbers of Tregs and programmed cell death protein 1 (PD-1) expression. In addition, sequential IL-2 administration rescued effective immune function, involving signal transducer and activator of transcription 1 (STAT1) activation. Importantly, IL-2 therapy significantly increased the frequency and function of HBV-specific CD8+ T cells, which translated into improved clinical outcomes, including HBeAg seroconversion, among the non-responder CHB patients. Our findings suggest that sequential IL-2 therapy shows efficacy in rescuing immune function in non-responder patients with refractory CHB.Dongyao WangBinqing FuXiaokun ShenChuang GuoYanyan LiuJunfei ZhangRui SunYing YeJiabin LiZhigang TianHaiming WeiNature Publishing GrouparticleMedicineRBiology (General)QH301-705.5ENSignal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-13 (2021) |
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DOAJ |
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Medicine R Biology (General) QH301-705.5 |
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Medicine R Biology (General) QH301-705.5 Dongyao Wang Binqing Fu Xiaokun Shen Chuang Guo Yanyan Liu Junfei Zhang Rui Sun Ying Ye Jiabin Li Zhigang Tian Haiming Wei Restoration of HBV-specific CD8+ T-cell responses by sequential low-dose IL-2 treatment in non-responder patients after IFN-α therapy |
| description |
Abstract Patients with chronic hepatitis B (CHB) undergoing interferon (IFN)-α-based therapies often exhibit a poor HBeAg serological response. Thus, there is an unmet need for new therapies aimed at CHB. This study comprised two clinical trials, including 130 CHB patients, who were treatment-naïve; in the first, 92 patients were systematically analyzed ex vivo for interleukin-2 receptor (IL-2R) expression and inhibitory molecules expression after receiving Peg-IFN-α-2b therapy. In our second clinical trial, 38 non-responder patients, in whom IFN-α therapy had failed, were treated with or without low-dose IL-2 for 24 weeks. We then examined the hepatitis B virus (HBV)-specific CD8+ T-cell response and the clinical outcome, in these patients. Although the majority of the participants undergoing Peg-IFN-α-2b therapy were non-responders, we observed a decrease in CD25 expression on their CD4+ T cells, suggesting that IFN-α therapy may provide a rationale for sequential IL-2 treatment without increasing regulatory T cells (Tregs). Following sequential therapy with IL-2, we demonstrated that the non-responders experienced a decrease in the numbers of Tregs and programmed cell death protein 1 (PD-1) expression. In addition, sequential IL-2 administration rescued effective immune function, involving signal transducer and activator of transcription 1 (STAT1) activation. Importantly, IL-2 therapy significantly increased the frequency and function of HBV-specific CD8+ T cells, which translated into improved clinical outcomes, including HBeAg seroconversion, among the non-responder CHB patients. Our findings suggest that sequential IL-2 therapy shows efficacy in rescuing immune function in non-responder patients with refractory CHB. |
| format |
article |
| author |
Dongyao Wang Binqing Fu Xiaokun Shen Chuang Guo Yanyan Liu Junfei Zhang Rui Sun Ying Ye Jiabin Li Zhigang Tian Haiming Wei |
| author_facet |
Dongyao Wang Binqing Fu Xiaokun Shen Chuang Guo Yanyan Liu Junfei Zhang Rui Sun Ying Ye Jiabin Li Zhigang Tian Haiming Wei |
| author_sort |
Dongyao Wang |
| title |
Restoration of HBV-specific CD8+ T-cell responses by sequential low-dose IL-2 treatment in non-responder patients after IFN-α therapy |
| title_short |
Restoration of HBV-specific CD8+ T-cell responses by sequential low-dose IL-2 treatment in non-responder patients after IFN-α therapy |
| title_full |
Restoration of HBV-specific CD8+ T-cell responses by sequential low-dose IL-2 treatment in non-responder patients after IFN-α therapy |
| title_fullStr |
Restoration of HBV-specific CD8+ T-cell responses by sequential low-dose IL-2 treatment in non-responder patients after IFN-α therapy |
| title_full_unstemmed |
Restoration of HBV-specific CD8+ T-cell responses by sequential low-dose IL-2 treatment in non-responder patients after IFN-α therapy |
| title_sort |
restoration of hbv-specific cd8+ t-cell responses by sequential low-dose il-2 treatment in non-responder patients after ifn-α therapy |
| publisher |
Nature Publishing Group |
| publishDate |
2021 |
| url |
https://doaj.org/article/21b417eb6d294715b19d0a664f3c43a8 |
| work_keys_str_mv |
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