PD-1 suppresses human CD38+ circulating Tfr cells and regulates humoral immunity
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 tit...
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| Language: | English |
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BMJ Publishing Group
2025-01-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/1/e010026.full |
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| author | Heng Zhang Hui Zheng Lin Guo Ying Tong Xiaolu Ma Yanchun Wang Renquan Lu Cuncun Chen Suhong Xie |
| author_facet | Heng Zhang Hui Zheng Lin Guo Ying Tong Xiaolu Ma Yanchun Wang Renquan Lu Cuncun Chen Suhong Xie |
| author_sort | Heng Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3b2f9b9a1d03474c855ce0cdd65e34f3 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-3b2f9b9a1d03474c855ce0cdd65e34f32025-01-14T23:15:13ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-01-0113110.1136/jitc-2024-010026PD-1 suppresses human CD38+ circulating Tfr cells and regulates humoral immunityHeng Zhang0Hui Zheng1Lin Guo2Ying Tong3Xiaolu Ma4Yanchun Wang5Renquan Lu6Cuncun Chen7Suhong Xie8School of Nursing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China3 Shanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Rehabilitation, Brain Hospital of Hunan Province, Changsha, China8 Neonatology, The Children’s Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Infectious Diseases, Kunming Children’s Hospital, Kunming, People`s Republic of ChinaDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, ChinaBackground 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.https://jitc.bmj.com/content/13/1/e010026.full |
| spellingShingle | Heng Zhang Hui Zheng Lin Guo Ying Tong Xiaolu Ma Yanchun Wang Renquan Lu Cuncun Chen Suhong Xie PD-1 suppresses human CD38+ circulating Tfr cells and regulates humoral immunity Journal for ImmunoTherapy of Cancer |
| title | PD-1 suppresses human CD38+ circulating Tfr cells and regulates humoral immunity |
| title_full | PD-1 suppresses human CD38+ circulating Tfr cells and regulates humoral immunity |
| title_fullStr | PD-1 suppresses human CD38+ circulating Tfr cells and regulates humoral immunity |
| title_full_unstemmed | PD-1 suppresses human CD38+ circulating Tfr cells and regulates humoral immunity |
| title_short | PD-1 suppresses human CD38+ circulating Tfr cells and regulates humoral immunity |
| title_sort | pd 1 suppresses human cd38 circulating tfr cells and regulates humoral immunity |
| url | https://jitc.bmj.com/content/13/1/e010026.full |
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