Breast cancer patient-derived scaffolds enhance the understanding of PD-L1 regulation and T cell cytotoxicity
Abstract Recent advances as well as obstacles for immune-based cancer treatment strategies, highlight the notable impact of patient cancer microenvironments on the immune cells and immune targets. Here, we use patient-derived scaffolds (PDS) generated from 110 primary breast cancers to monitor the i...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08054-3 |
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| _version_ | 1850181309865918464 |
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| author | Elena Garre Sara Rhost Anna Gustafsson Louis Szeponik Thais Fenz Araujo Marianne Quiding-Järbrink Khalil Helou Anders Ståhlberg Göran Landberg |
| author_facet | Elena Garre Sara Rhost Anna Gustafsson Louis Szeponik Thais Fenz Araujo Marianne Quiding-Järbrink Khalil Helou Anders Ståhlberg Göran Landberg |
| author_sort | Elena Garre |
| collection | DOAJ |
| description | Abstract Recent advances as well as obstacles for immune-based cancer treatment strategies, highlight the notable impact of patient cancer microenvironments on the immune cells and immune targets. Here, we use patient-derived scaffolds (PDS) generated from 110 primary breast cancers to monitor the impact of the cancer microenvironment on immune regulators. Pronounced variation in PD-L1 expression is observed in cancer cells adapted to different patient scaffolds. This variation is further linked to clinical observations and correlated with specific proteins detected in the cell-free PDSs using mass spectrometry. When adding T cells to the PDS-based cancer cultures, the killing efficiency of activated T cells vary between the cultures, whereas non-activated T cells modulate the cancer cell PD-L1 expression to treatment-predictive values, matching killing capacities of activated T cells. Surviving cancer cells show enrichment in cancer stem cell and epithelial-to-mesenchymal transition (EMT) features, suggesting that T cells may not efficiently target cells with metastatic potential. We conclude that clinically relevant insights in how to optimally target and guide immune-based cancer therapies can be obtained by including patient-derived scaffolds and cues from the cancer microenvironment in cancer patient handling and drug development. |
| format | Article |
| id | doaj-art-3c6b3ba7a9e9431ab04b9a7bc033a2a9 |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-3c6b3ba7a9e9431ab04b9a7bc033a2a92025-08-20T02:17:56ZengNature PortfolioCommunications Biology2399-36422025-04-018111210.1038/s42003-025-08054-3Breast cancer patient-derived scaffolds enhance the understanding of PD-L1 regulation and T cell cytotoxicityElena Garre0Sara Rhost1Anna Gustafsson2Louis Szeponik3Thais Fenz Araujo4Marianne Quiding-Järbrink5Khalil Helou6Anders Ståhlberg7Göran Landberg8Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, Sahlgrenska Center for Cancer Research, University of GothenburgDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, Sahlgrenska Center for Cancer Research, University of GothenburgDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, Sahlgrenska Center for Cancer Research, University of GothenburgDepartment of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of GothenburgDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, Sahlgrenska Center for Cancer Research, University of GothenburgDepartment of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of GothenburgDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of GothenburgDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, Sahlgrenska Center for Cancer Research, University of GothenburgDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, Sahlgrenska Center for Cancer Research, University of GothenburgAbstract Recent advances as well as obstacles for immune-based cancer treatment strategies, highlight the notable impact of patient cancer microenvironments on the immune cells and immune targets. Here, we use patient-derived scaffolds (PDS) generated from 110 primary breast cancers to monitor the impact of the cancer microenvironment on immune regulators. Pronounced variation in PD-L1 expression is observed in cancer cells adapted to different patient scaffolds. This variation is further linked to clinical observations and correlated with specific proteins detected in the cell-free PDSs using mass spectrometry. When adding T cells to the PDS-based cancer cultures, the killing efficiency of activated T cells vary between the cultures, whereas non-activated T cells modulate the cancer cell PD-L1 expression to treatment-predictive values, matching killing capacities of activated T cells. Surviving cancer cells show enrichment in cancer stem cell and epithelial-to-mesenchymal transition (EMT) features, suggesting that T cells may not efficiently target cells with metastatic potential. We conclude that clinically relevant insights in how to optimally target and guide immune-based cancer therapies can be obtained by including patient-derived scaffolds and cues from the cancer microenvironment in cancer patient handling and drug development.https://doi.org/10.1038/s42003-025-08054-3 |
| spellingShingle | Elena Garre Sara Rhost Anna Gustafsson Louis Szeponik Thais Fenz Araujo Marianne Quiding-Järbrink Khalil Helou Anders Ståhlberg Göran Landberg Breast cancer patient-derived scaffolds enhance the understanding of PD-L1 regulation and T cell cytotoxicity Communications Biology |
| title | Breast cancer patient-derived scaffolds enhance the understanding of PD-L1 regulation and T cell cytotoxicity |
| title_full | Breast cancer patient-derived scaffolds enhance the understanding of PD-L1 regulation and T cell cytotoxicity |
| title_fullStr | Breast cancer patient-derived scaffolds enhance the understanding of PD-L1 regulation and T cell cytotoxicity |
| title_full_unstemmed | Breast cancer patient-derived scaffolds enhance the understanding of PD-L1 regulation and T cell cytotoxicity |
| title_short | Breast cancer patient-derived scaffolds enhance the understanding of PD-L1 regulation and T cell cytotoxicity |
| title_sort | breast cancer patient derived scaffolds enhance the understanding of pd l1 regulation and t cell cytotoxicity |
| url | https://doi.org/10.1038/s42003-025-08054-3 |
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