Activated B cells suppress T-cell function through metabolic competition
Background B cells play a pivotal role in regulating the immune response. The induction of B cell-mediated immunosuppressive function requires B cell activating signals. However, the mechanisms by which activated B cells mediate T-cell suppression are not fully understood.Methods We investigated the...
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| Language: | English |
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BMJ Publishing Group
2022-12-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/12/e005644.full |
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| author | Li Li Michael Green Fang Wang Ye Li Jennifer Wargo Marina Konopleva Elizabeth J Shpall Rafet Basar May Daher Ana Karen Nunez Cortes Hila Shaim Natalia Baran Ken Chen Luis Muniz-Feliciano Nobuhiko Imahashi Yuefan Huang Pinaki Prosad Banerjee Junjun Lu Nadima Uprety Emily Ensley Tamara J Laskowski Judy S Moyes Mayela Mendt Lucila N Kerbauy Mayra Shanley Francesca Lorraine Wei Inng Lim Katayoun Rezvani |
| author_facet | Li Li Michael Green Fang Wang Ye Li Jennifer Wargo Marina Konopleva Elizabeth J Shpall Rafet Basar May Daher Ana Karen Nunez Cortes Hila Shaim Natalia Baran Ken Chen Luis Muniz-Feliciano Nobuhiko Imahashi Yuefan Huang Pinaki Prosad Banerjee Junjun Lu Nadima Uprety Emily Ensley Tamara J Laskowski Judy S Moyes Mayela Mendt Lucila N Kerbauy Mayra Shanley Francesca Lorraine Wei Inng Lim Katayoun Rezvani |
| author_sort | Li Li |
| collection | DOAJ |
| description | Background B cells play a pivotal role in regulating the immune response. The induction of B cell-mediated immunosuppressive function requires B cell activating signals. However, the mechanisms by which activated B cells mediate T-cell suppression are not fully understood.Methods We investigated the potential contribution of metabolic activity of activated B cells to T-cell suppression by performing in vitro experiments and by analyzing clinical samples using mass cytometry and single-cell RNA sequencing.Results Here we show that following activation, B cells acquire an immunoregulatory phenotype and promote T-cell suppression by metabolic competition. Activated B cells induced hypoxia in T cells in a cell–cell contact dependent manner by consuming more oxygen via an increase in their oxidative phosphorylation (OXPHOS). Moreover, activated B cells deprived T cells of glucose and produced lactic acid through their high glycolytic activity. Activated B cells thus inhibited the mammalian target of rapamycin pathway in T cells, resulting in suppression of T-cell cytokine production and proliferation. Finally, we confirmed the presence of tumor-associated B cells with high glycolytic and OXPHOS activities in patients with melanoma, associated with poor response to immune checkpoint blockade therapy.Conclusions We have revealed for the first time the immunomodulatory effects of the metabolic activity of activated B cells and their possible role in suppressing antitumor T-cell responses. These findings add novel insights into immunometabolism and have important implications for cancer immunotherapy. |
| format | Article |
| id | doaj-art-d3edf7d013de4e0baf660853daac9cb7 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-d3edf7d013de4e0baf660853daac9cb72024-11-24T02:20:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-12-01101210.1136/jitc-2022-005644Activated B cells suppress T-cell function through metabolic competitionLi Li0Michael Green1Fang Wang2Ye Li3Jennifer Wargo4Marina Konopleva5Elizabeth J Shpall6Rafet Basar7May Daher8Ana Karen Nunez Cortes9Hila Shaim10Natalia Baran11Ken Chen12Luis Muniz-Feliciano13Nobuhiko Imahashi14Yuefan Huang15Pinaki Prosad Banerjee16Junjun Lu17Nadima Uprety18Emily Ensley19Tamara J Laskowski20Judy S Moyes21Mayela Mendt22Lucila N Kerbauy23Mayra Shanley24Francesca Lorraine Wei Inng Lim25Katayoun Rezvani26Department of Nursing, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, ChinaDepartment of Family Medicine, Queen`s University, Kingston, Ontario, CanadaDepartment of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, ChinaDepartment of Ophthalmology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, Guangdong, ChinaDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA22 Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA1The University of Texas MDACC, Houston, USAUniversity of Texas MD Anderson Cancer Center, Houston, Texas, USA1The University of Texas MDACC, Houston, USA1The University of Texas MDACC, Houston, USADepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA1The University of Texas MDACC, Houston, USA1The University of Texas MDACC, Houston, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USABackground B cells play a pivotal role in regulating the immune response. The induction of B cell-mediated immunosuppressive function requires B cell activating signals. However, the mechanisms by which activated B cells mediate T-cell suppression are not fully understood.Methods We investigated the potential contribution of metabolic activity of activated B cells to T-cell suppression by performing in vitro experiments and by analyzing clinical samples using mass cytometry and single-cell RNA sequencing.Results Here we show that following activation, B cells acquire an immunoregulatory phenotype and promote T-cell suppression by metabolic competition. Activated B cells induced hypoxia in T cells in a cell–cell contact dependent manner by consuming more oxygen via an increase in their oxidative phosphorylation (OXPHOS). Moreover, activated B cells deprived T cells of glucose and produced lactic acid through their high glycolytic activity. Activated B cells thus inhibited the mammalian target of rapamycin pathway in T cells, resulting in suppression of T-cell cytokine production and proliferation. Finally, we confirmed the presence of tumor-associated B cells with high glycolytic and OXPHOS activities in patients with melanoma, associated with poor response to immune checkpoint blockade therapy.Conclusions We have revealed for the first time the immunomodulatory effects of the metabolic activity of activated B cells and their possible role in suppressing antitumor T-cell responses. These findings add novel insights into immunometabolism and have important implications for cancer immunotherapy.https://jitc.bmj.com/content/10/12/e005644.full |
| spellingShingle | Li Li Michael Green Fang Wang Ye Li Jennifer Wargo Marina Konopleva Elizabeth J Shpall Rafet Basar May Daher Ana Karen Nunez Cortes Hila Shaim Natalia Baran Ken Chen Luis Muniz-Feliciano Nobuhiko Imahashi Yuefan Huang Pinaki Prosad Banerjee Junjun Lu Nadima Uprety Emily Ensley Tamara J Laskowski Judy S Moyes Mayela Mendt Lucila N Kerbauy Mayra Shanley Francesca Lorraine Wei Inng Lim Katayoun Rezvani Activated B cells suppress T-cell function through metabolic competition Journal for ImmunoTherapy of Cancer |
| title | Activated B cells suppress T-cell function through metabolic competition |
| title_full | Activated B cells suppress T-cell function through metabolic competition |
| title_fullStr | Activated B cells suppress T-cell function through metabolic competition |
| title_full_unstemmed | Activated B cells suppress T-cell function through metabolic competition |
| title_short | Activated B cells suppress T-cell function through metabolic competition |
| title_sort | activated b cells suppress t cell function through metabolic competition |
| url | https://jitc.bmj.com/content/10/12/e005644.full |
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