Altered immune signatures in breast cancer lymph nodes with metastases revealed by spatial proteome analyses
Abstract Background Metastasis to lymph nodes is strongly associated with reduced survival in breast cancer patients. To increase the understanding on how lymph node metastasis impairs the local immune response in affected lymph nodes, we here studied spatial proteomic changes of critical lymph node...
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BMC
2025-04-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06415-4 |
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| author | Oscar Briem Balázs Tahin Asger Meldgaard Frank Lina Olsson Anna Sandström Gerdtsson Eva Källberg Karin Leandersson |
| author_facet | Oscar Briem Balázs Tahin Asger Meldgaard Frank Lina Olsson Anna Sandström Gerdtsson Eva Källberg Karin Leandersson |
| author_sort | Oscar Briem |
| collection | DOAJ |
| description | Abstract Background Metastasis to lymph nodes is strongly associated with reduced survival in breast cancer patients. To increase the understanding on how lymph node metastasis impairs the local immune response in affected lymph nodes, we here studied spatial proteomic changes of critical lymph node immune populations in uninvolved lymph nodes (UnLN) and paired lymph nodes with metastases (LNM) from five breast cancer patients. Methods The proteome was analyzed for cortical lymphocyte compartments, subcapsular sinus (SCS) and medullary sinus (MS) CD169+ macrophages, using the Digital Spatial Profiling (DSP) platform from NanoString. Results Our results identified a stable proteome of SCS CD169+ macrophages in LNM, with the exception for downregulation of the anti-apoptotic protein Bcl-xL and FAPα, but a clear reduction in numbers of SCS CD169+ macrophages in LNM. In contrast, the proteome of MS CD169+ macrophages, B-cell compartments and interfollicular T-cells showed altered immune signatures in LNM, indicating that the decline in SCS CD169+ macrophages coincide with a malfunction in the local, anti-tumor immune responses. Conclusions The findings from our study support the notion that metastasis to lymph nodes in breast cancer patients modifies local immune responses. These changes may contribute to explain unsuccessful therapeutic responses, and thereby worsened prognosis, for breast cancer patients with LNM. |
| format | Article |
| id | doaj-art-6fb2f2a7f4e649328871d4b5ef7ebe3c |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-6fb2f2a7f4e649328871d4b5ef7ebe3c2025-08-20T03:46:12ZengBMCJournal of Translational Medicine1479-58762025-04-0123111410.1186/s12967-025-06415-4Altered immune signatures in breast cancer lymph nodes with metastases revealed by spatial proteome analysesOscar Briem0Balázs Tahin1Asger Meldgaard Frank2Lina Olsson3Anna Sandström Gerdtsson4Eva Källberg5Karin Leandersson6Cancer Immunology, Department for Translational Medicine, Clinical Research Center, Lund UniversityDivision of Clinical Pathology, Department of Clinical Sciences, Lund UniversityDivision of Immunotechnology, Faculty of Engineering, Lund UniversityDivision of Immunotechnology, Faculty of Engineering, Lund UniversityDivision of Immunotechnology, Faculty of Engineering, Lund UniversityCancer Immunology, Department for Translational Medicine, Clinical Research Center, Lund UniversityCancer Immunology, Department for Translational Medicine, Clinical Research Center, Lund UniversityAbstract Background Metastasis to lymph nodes is strongly associated with reduced survival in breast cancer patients. To increase the understanding on how lymph node metastasis impairs the local immune response in affected lymph nodes, we here studied spatial proteomic changes of critical lymph node immune populations in uninvolved lymph nodes (UnLN) and paired lymph nodes with metastases (LNM) from five breast cancer patients. Methods The proteome was analyzed for cortical lymphocyte compartments, subcapsular sinus (SCS) and medullary sinus (MS) CD169+ macrophages, using the Digital Spatial Profiling (DSP) platform from NanoString. Results Our results identified a stable proteome of SCS CD169+ macrophages in LNM, with the exception for downregulation of the anti-apoptotic protein Bcl-xL and FAPα, but a clear reduction in numbers of SCS CD169+ macrophages in LNM. In contrast, the proteome of MS CD169+ macrophages, B-cell compartments and interfollicular T-cells showed altered immune signatures in LNM, indicating that the decline in SCS CD169+ macrophages coincide with a malfunction in the local, anti-tumor immune responses. Conclusions The findings from our study support the notion that metastasis to lymph nodes in breast cancer patients modifies local immune responses. These changes may contribute to explain unsuccessful therapeutic responses, and thereby worsened prognosis, for breast cancer patients with LNM.https://doi.org/10.1186/s12967-025-06415-4Breast cancerLymph node metastasisCD169+ macrophagesB-cell folliclesGerminal centersInterfollicular T-cells |
| spellingShingle | Oscar Briem Balázs Tahin Asger Meldgaard Frank Lina Olsson Anna Sandström Gerdtsson Eva Källberg Karin Leandersson Altered immune signatures in breast cancer lymph nodes with metastases revealed by spatial proteome analyses Journal of Translational Medicine Breast cancer Lymph node metastasis CD169+ macrophages B-cell follicles Germinal centers Interfollicular T-cells |
| title | Altered immune signatures in breast cancer lymph nodes with metastases revealed by spatial proteome analyses |
| title_full | Altered immune signatures in breast cancer lymph nodes with metastases revealed by spatial proteome analyses |
| title_fullStr | Altered immune signatures in breast cancer lymph nodes with metastases revealed by spatial proteome analyses |
| title_full_unstemmed | Altered immune signatures in breast cancer lymph nodes with metastases revealed by spatial proteome analyses |
| title_short | Altered immune signatures in breast cancer lymph nodes with metastases revealed by spatial proteome analyses |
| title_sort | altered immune signatures in breast cancer lymph nodes with metastases revealed by spatial proteome analyses |
| topic | Breast cancer Lymph node metastasis CD169+ macrophages B-cell follicles Germinal centers Interfollicular T-cells |
| url | https://doi.org/10.1186/s12967-025-06415-4 |
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