The interaction between the soluble programmed death ligand-1 (sPD-L1) and PD-1+ regulator B cells mediates immunosuppression in triple-negative breast cancer
Accumulating evidence suggests that regulatory B cells (Bregs) play important roles in inhibiting the immune response in tumors. Programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) are important molecules that maintain the balance of the immune response and immune tolerance. This study a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.830606/full |
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| author | Xuejiao Li Xuejiao Li Huan Du Huan Du Shenghua Zhan Wenting Liu Wenting Liu Zhangyu Wang Zhangyu Wang Jing Lan Longxiang PuYang Yuqiu Wan Yuqiu Wan Qiuxia Qu Sining Wang Yang Yang Qin Wang Fang Xie |
| author_facet | Xuejiao Li Xuejiao Li Huan Du Huan Du Shenghua Zhan Wenting Liu Wenting Liu Zhangyu Wang Zhangyu Wang Jing Lan Longxiang PuYang Yuqiu Wan Yuqiu Wan Qiuxia Qu Sining Wang Yang Yang Qin Wang Fang Xie |
| author_sort | Xuejiao Li |
| collection | DOAJ |
| description | Accumulating evidence suggests that regulatory B cells (Bregs) play important roles in inhibiting the immune response in tumors. Programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) are important molecules that maintain the balance of the immune response and immune tolerance. This study aims to evaluate the soluble form of PD-L1 and its function in inducing the differentiation of B lymphocytes, investigate the relationship between soluble PD-L1 (sPD-L1) and B-cell subsets, and explore the antitumor activity of T lymphocytes after PD-L1 blockade in coculture systems. In an effort to explore the role of sPD-L1 in human breast cancer etiology, we examined the levels of sPD-L1 and interleukin-10 (IL-10) in the serum of breast tumor patients and the proportions of B cells, PD-1+ B cells, Bregs, and PD-1+ Bregs in the peripheral blood of patients with breast tumors and assessed their relationship among sPD-L1, IL-10, and B-cell subsets. The levels of sPD-L1 and IL-10 in serum were found to be significantly higher in invasive breast cancer (IBCa) patients than in breast fibroadenoma (FIBma) patients. Meanwhile, the proportions and absolute numbers of Bregs and PD-1+ Bregs in the peripheral blood of IBCa patients were significantly higher than those of FIBma patients. Notably, they were the highest in triple-negative breast cancer (TNBC) among other subtypes of IBCa. Positive correlations of sPD-L1 and IL-10, IL-10 and PD-1+ Bregs, and also sPD-L1 and PD-1+ Bregs were observed in IBCa. We further demonstrated that sPD-L1 could induce Breg differentiation, IL-10 secretion, and IL-10 mRNA expression in a dose-dependent manner in vitro. Finally, the induction of regulatory T cells (Tregs) by Bregs was further shown to suppress the antitumor response and that PD-L1 blockade therapies could promote the apoptosis of tumor cells. Together, these results indicated that sPD-L1 could mediate the differentiation of Bregs, expand CD4+ Tregs and weaken the antitumor activity of CD4+ T cells. PD-L1/PD-1 blockade therapies might be a powerful therapeutic strategy for IBCa patients, particularly for TNBC patients with high level of PD-1+ Bregs. |
| first_indexed | 2024-04-13T03:27:27Z |
| format | Article |
| id | doaj.art-a35c342d69de4bb9995362b1c476c263 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T03:27:27Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-a35c342d69de4bb9995362b1c476c2632022-12-22T03:04:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.830606830606The interaction between the soluble programmed death ligand-1 (sPD-L1) and PD-1+ regulator B cells mediates immunosuppression in triple-negative breast cancerXuejiao Li0Xuejiao Li1Huan Du2Huan Du3Shenghua Zhan4Wenting Liu5Wenting Liu6Zhangyu Wang7Zhangyu Wang8Jing Lan9Longxiang PuYang10Yuqiu Wan11Yuqiu Wan12Qiuxia Qu13Sining Wang14Yang Yang15Qin Wang16Fang Xie17School of Biology & Basic Medical Sciences, Medical College of Soochow University, Suzhou, ChinaDepartment of Pathology, The First People’s Hospital of Lianyungang, Lianyungang, ChinaSchool of Biology & Basic Medical Sciences, Medical College of Soochow University, Suzhou, ChinaDepartment of Pathology, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaSchool of Biology & Basic Medical Sciences, Medical College of Soochow University, Suzhou, ChinaDepartment of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of General Surgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, ChinaDepartment of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaSchool of Biology & Basic Medical Sciences, Medical College of Soochow University, Suzhou, ChinaSchool of Biology & Basic Medical Sciences, Medical College of Soochow University, Suzhou, ChinaDepartment of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaSchool of Biology & Basic Medical Sciences, Medical College of Soochow University, Suzhou, ChinaSchool of Biology & Basic Medical Sciences, Medical College of Soochow University, Suzhou, ChinaSchool of Biology & Basic Medical Sciences, Medical College of Soochow University, Suzhou, ChinaSchool of Biology & Basic Medical Sciences, Medical College of Soochow University, Suzhou, ChinaAccumulating evidence suggests that regulatory B cells (Bregs) play important roles in inhibiting the immune response in tumors. Programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) are important molecules that maintain the balance of the immune response and immune tolerance. This study aims to evaluate the soluble form of PD-L1 and its function in inducing the differentiation of B lymphocytes, investigate the relationship between soluble PD-L1 (sPD-L1) and B-cell subsets, and explore the antitumor activity of T lymphocytes after PD-L1 blockade in coculture systems. In an effort to explore the role of sPD-L1 in human breast cancer etiology, we examined the levels of sPD-L1 and interleukin-10 (IL-10) in the serum of breast tumor patients and the proportions of B cells, PD-1+ B cells, Bregs, and PD-1+ Bregs in the peripheral blood of patients with breast tumors and assessed their relationship among sPD-L1, IL-10, and B-cell subsets. The levels of sPD-L1 and IL-10 in serum were found to be significantly higher in invasive breast cancer (IBCa) patients than in breast fibroadenoma (FIBma) patients. Meanwhile, the proportions and absolute numbers of Bregs and PD-1+ Bregs in the peripheral blood of IBCa patients were significantly higher than those of FIBma patients. Notably, they were the highest in triple-negative breast cancer (TNBC) among other subtypes of IBCa. Positive correlations of sPD-L1 and IL-10, IL-10 and PD-1+ Bregs, and also sPD-L1 and PD-1+ Bregs were observed in IBCa. We further demonstrated that sPD-L1 could induce Breg differentiation, IL-10 secretion, and IL-10 mRNA expression in a dose-dependent manner in vitro. Finally, the induction of regulatory T cells (Tregs) by Bregs was further shown to suppress the antitumor response and that PD-L1 blockade therapies could promote the apoptosis of tumor cells. Together, these results indicated that sPD-L1 could mediate the differentiation of Bregs, expand CD4+ Tregs and weaken the antitumor activity of CD4+ T cells. PD-L1/PD-1 blockade therapies might be a powerful therapeutic strategy for IBCa patients, particularly for TNBC patients with high level of PD-1+ Bregs.https://www.frontiersin.org/articles/10.3389/fimmu.2022.830606/fullsPD-L1PD-1+ regulator B cellsregulator T cellimmunosuppressionthe triple-negative breast cancer |
| spellingShingle | Xuejiao Li Xuejiao Li Huan Du Huan Du Shenghua Zhan Wenting Liu Wenting Liu Zhangyu Wang Zhangyu Wang Jing Lan Longxiang PuYang Yuqiu Wan Yuqiu Wan Qiuxia Qu Sining Wang Yang Yang Qin Wang Fang Xie The interaction between the soluble programmed death ligand-1 (sPD-L1) and PD-1+ regulator B cells mediates immunosuppression in triple-negative breast cancer Frontiers in Immunology sPD-L1 PD-1+ regulator B cells regulator T cell immunosuppression the triple-negative breast cancer |
| title | The interaction between the soluble programmed death ligand-1 (sPD-L1) and PD-1+ regulator B cells mediates immunosuppression in triple-negative breast cancer |
| title_full | The interaction between the soluble programmed death ligand-1 (sPD-L1) and PD-1+ regulator B cells mediates immunosuppression in triple-negative breast cancer |
| title_fullStr | The interaction between the soluble programmed death ligand-1 (sPD-L1) and PD-1+ regulator B cells mediates immunosuppression in triple-negative breast cancer |
| title_full_unstemmed | The interaction between the soluble programmed death ligand-1 (sPD-L1) and PD-1+ regulator B cells mediates immunosuppression in triple-negative breast cancer |
| title_short | The interaction between the soluble programmed death ligand-1 (sPD-L1) and PD-1+ regulator B cells mediates immunosuppression in triple-negative breast cancer |
| title_sort | interaction between the soluble programmed death ligand 1 spd l1 and pd 1 regulator b cells mediates immunosuppression in triple negative breast cancer |
| topic | sPD-L1 PD-1+ regulator B cells regulator T cell immunosuppression the triple-negative breast cancer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.830606/full |
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