B cells enhance IL-1 beta driven invasiveness in triple negative breast cancer
Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype often characterized by high lymphocyte infiltration, including tumor-infiltrating B cells (TIBs). These cells are present even in early stages of TNBC and associated with microinvasion. This study shows that co-culturing TNBC cel...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-86064-1 |
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| author | Nicole J. Toney Lynn M. Opdenaker Lisa Frerichs Shirin R. Modarai Aihui Ma Holly Archinal Grace O. Ajayi Jennifer Sims-Mourtada |
| author_facet | Nicole J. Toney Lynn M. Opdenaker Lisa Frerichs Shirin R. Modarai Aihui Ma Holly Archinal Grace O. Ajayi Jennifer Sims-Mourtada |
| author_sort | Nicole J. Toney |
| collection | DOAJ |
| description | Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype often characterized by high lymphocyte infiltration, including tumor-infiltrating B cells (TIBs). These cells are present even in early stages of TNBC and associated with microinvasion. This study shows that co-culturing TNBC cells with B cells increases Interleukin-1β (IL-1β) expression and secretion. We further show that B cell-induced IL-1β activates NFκB signaling, leading to higher expression of target genes and promoting IL-1β-dependent increases in matrix metalloproteinase (MMP) activity, invasion, and migration. Immunohistochemical analysis of IL-1β and TIBs in triple-negative ductal carcinoma in situ (DCIS, n = 90) and invasive TNBC (n = 171) revealed that in DCIS, TIBs correlated with IL-1β expression and microinvasion, with IL-1β also linked to recurrence. In invasive TNBC, IL-1β expression correlated with TIB density and stage, with high IL-1β levels associated with poorer survival outcomes. These findings suggest that early B cell presence in TNBC can induce IL-1β secretion, enhancing invasion and mobility through IL-1β-NFκB signaling. This highlights the potential of IL-1 inhibitors as preventive and therapeutic options for hormone receptor-negative DCIS and TNBC. |
| format | Article |
| id | doaj-art-4191edd484bb4da2be72333a6e8f1ba2 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-4191edd484bb4da2be72333a6e8f1ba22025-01-19T12:23:17ZengNature PortfolioScientific Reports2045-23222025-01-0115111610.1038/s41598-025-86064-1B cells enhance IL-1 beta driven invasiveness in triple negative breast cancerNicole J. Toney0Lynn M. Opdenaker1Lisa Frerichs2Shirin R. Modarai3Aihui Ma4Holly Archinal5Grace O. Ajayi6Jennifer Sims-Mourtada7Cawley Center for Translational Cancer Research, Helen F. Graham Cancer Center and Research Institute Christiana Care Health Services, Inc.Cawley Center for Translational Cancer Research, Helen F. Graham Cancer Center and Research Institute Christiana Care Health Services, Inc.Cawley Center for Translational Cancer Research, Helen F. Graham Cancer Center and Research Institute Christiana Care Health Services, Inc.Cawley Center for Translational Cancer Research, Helen F. Graham Cancer Center and Research Institute Christiana Care Health Services, Inc.Cawley Center for Translational Cancer Research, Helen F. Graham Cancer Center and Research Institute Christiana Care Health Services, Inc.Cawley Center for Translational Cancer Research, Helen F. Graham Cancer Center and Research Institute Christiana Care Health Services, Inc.Cawley Center for Translational Cancer Research, Helen F. Graham Cancer Center and Research Institute Christiana Care Health Services, Inc.Cawley Center for Translational Cancer Research, Helen F. Graham Cancer Center and Research Institute Christiana Care Health Services, Inc.Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype often characterized by high lymphocyte infiltration, including tumor-infiltrating B cells (TIBs). These cells are present even in early stages of TNBC and associated with microinvasion. This study shows that co-culturing TNBC cells with B cells increases Interleukin-1β (IL-1β) expression and secretion. We further show that B cell-induced IL-1β activates NFκB signaling, leading to higher expression of target genes and promoting IL-1β-dependent increases in matrix metalloproteinase (MMP) activity, invasion, and migration. Immunohistochemical analysis of IL-1β and TIBs in triple-negative ductal carcinoma in situ (DCIS, n = 90) and invasive TNBC (n = 171) revealed that in DCIS, TIBs correlated with IL-1β expression and microinvasion, with IL-1β also linked to recurrence. In invasive TNBC, IL-1β expression correlated with TIB density and stage, with high IL-1β levels associated with poorer survival outcomes. These findings suggest that early B cell presence in TNBC can induce IL-1β secretion, enhancing invasion and mobility through IL-1β-NFκB signaling. This highlights the potential of IL-1 inhibitors as preventive and therapeutic options for hormone receptor-negative DCIS and TNBC.https://doi.org/10.1038/s41598-025-86064-1Breast cancerTriple negative breast cancerInterleukin 1 betaB cellsNFkappa B |
| spellingShingle | Nicole J. Toney Lynn M. Opdenaker Lisa Frerichs Shirin R. Modarai Aihui Ma Holly Archinal Grace O. Ajayi Jennifer Sims-Mourtada B cells enhance IL-1 beta driven invasiveness in triple negative breast cancer Scientific Reports Breast cancer Triple negative breast cancer Interleukin 1 beta B cells NFkappa B |
| title | B cells enhance IL-1 beta driven invasiveness in triple negative breast cancer |
| title_full | B cells enhance IL-1 beta driven invasiveness in triple negative breast cancer |
| title_fullStr | B cells enhance IL-1 beta driven invasiveness in triple negative breast cancer |
| title_full_unstemmed | B cells enhance IL-1 beta driven invasiveness in triple negative breast cancer |
| title_short | B cells enhance IL-1 beta driven invasiveness in triple negative breast cancer |
| title_sort | b cells enhance il 1 beta driven invasiveness in triple negative breast cancer |
| topic | Breast cancer Triple negative breast cancer Interleukin 1 beta B cells NFkappa B |
| url | https://doi.org/10.1038/s41598-025-86064-1 |
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