Divergent therapeutic and prognostic impacts of immunogenic features in undifferentiated pleomorphic sarcoma and myxofibrosarcoma
Abstract Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are genetically complex soft tissue sarcomas with distinct morphological features. Treatment typically involves surgery, often combined with neoadjuvant chemo- or radiotherapy. To better understand the immunobiology of th...
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2025-07-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-04123-y |
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| author | Siddh van Oost Debora M. Meijer Zeynep B. Erdem Marieke E. IJsselsteijn Jessica Roelands Suk Wai Lam Melissa S. Boejharat Brendy E. W. M. van den Akker Ruud van der Breggen Inge H. Briare-de Bruijn Lukas J. A. C. Hawinkels Anouk A. Kruiswijk Manon van der Ploeg Pauline M. Wijers-Koster Rick L. Haas Michiel A. J. van den Sande Noel F. C. C. de Miranda Judith V. M. G. Bovee |
| author_facet | Siddh van Oost Debora M. Meijer Zeynep B. Erdem Marieke E. IJsselsteijn Jessica Roelands Suk Wai Lam Melissa S. Boejharat Brendy E. W. M. van den Akker Ruud van der Breggen Inge H. Briare-de Bruijn Lukas J. A. C. Hawinkels Anouk A. Kruiswijk Manon van der Ploeg Pauline M. Wijers-Koster Rick L. Haas Michiel A. J. van den Sande Noel F. C. C. de Miranda Judith V. M. G. Bovee |
| author_sort | Siddh van Oost |
| collection | DOAJ |
| description | Abstract Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are genetically complex soft tissue sarcomas with distinct morphological features. Treatment typically involves surgery, often combined with neoadjuvant chemo- or radiotherapy. To better understand the immunobiology of these sarcomas and its associations with treatment response and prognosis, we performed transcriptomic and immunophenotypic profiling. RNA sequencing was performed on 13 UPS and 10 MFS, and immunological profiles were compared with soft tissue sarcoma data from The Cancer Genome Atlas (n = 206 including 44 UPS and 17 MFS). Immune contextures were further evaluated in 14 UPS and 15 MFS using imaging mass cytometry. Characterization of T cell and macrophage infiltration in tumors was further assessed in 23 UPS and 22 MFS through multispectral immunofluorescence and immunohistochemical analysis. UPS and MFS demonstrated immunogenic features compared to other soft tissue sarcomas, with subsets of UPS and MFS demonstrating high T cell infiltration, while UPS demonstrated a higher infiltration by myeloid cells as compared to MFS. Prognostically, T cells and CD68+CD163+ macrophages were associated with metastasis-free survival in UPS but not in MFS. Notably, in UPS, neoadjuvant radiotherapy appeared to induce cytotoxic T cell infiltration and depletion of myeloid cells, whereas these effects were not observed in MFS. These findings highlight important differences in the immunobiology of UPS and MFS with therapeutic and prognostic implications. These differences should be taken into account given the growing availability of immunotherapeutic options for treating patients with soft tissue sarcomas. |
| format | Article |
| id | doaj-art-b529a166eb844cbebaf3318a52c5e51d |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-b529a166eb844cbebaf3318a52c5e51d2025-08-20T04:02:57ZengSpringerCancer Immunology, Immunotherapy1432-08512025-07-0174811410.1007/s00262-025-04123-yDivergent therapeutic and prognostic impacts of immunogenic features in undifferentiated pleomorphic sarcoma and myxofibrosarcomaSiddh van Oost0Debora M. Meijer1Zeynep B. Erdem2Marieke E. IJsselsteijn3Jessica Roelands4Suk Wai Lam5Melissa S. Boejharat6Brendy E. W. M. van den Akker7Ruud van der Breggen8Inge H. Briare-de Bruijn9Lukas J. A. C. Hawinkels10Anouk A. Kruiswijk11Manon van der Ploeg12Pauline M. Wijers-Koster13Rick L. Haas14Michiel A. J. van den Sande15Noel F. C. C. de Miranda16Judith V. M. G. Bovee17Department of Pathology, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDepartment of Gastroenterology and Hepatology, Leiden University Medical CenterDepartment of Orthopedic Surgery, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDepartment of Radiotherapy, The Netherlands Cancer InstituteDepartment of Orthopedic Surgery, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterAbstract Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are genetically complex soft tissue sarcomas with distinct morphological features. Treatment typically involves surgery, often combined with neoadjuvant chemo- or radiotherapy. To better understand the immunobiology of these sarcomas and its associations with treatment response and prognosis, we performed transcriptomic and immunophenotypic profiling. RNA sequencing was performed on 13 UPS and 10 MFS, and immunological profiles were compared with soft tissue sarcoma data from The Cancer Genome Atlas (n = 206 including 44 UPS and 17 MFS). Immune contextures were further evaluated in 14 UPS and 15 MFS using imaging mass cytometry. Characterization of T cell and macrophage infiltration in tumors was further assessed in 23 UPS and 22 MFS through multispectral immunofluorescence and immunohistochemical analysis. UPS and MFS demonstrated immunogenic features compared to other soft tissue sarcomas, with subsets of UPS and MFS demonstrating high T cell infiltration, while UPS demonstrated a higher infiltration by myeloid cells as compared to MFS. Prognostically, T cells and CD68+CD163+ macrophages were associated with metastasis-free survival in UPS but not in MFS. Notably, in UPS, neoadjuvant radiotherapy appeared to induce cytotoxic T cell infiltration and depletion of myeloid cells, whereas these effects were not observed in MFS. These findings highlight important differences in the immunobiology of UPS and MFS with therapeutic and prognostic implications. These differences should be taken into account given the growing availability of immunotherapeutic options for treating patients with soft tissue sarcomas.https://doi.org/10.1007/s00262-025-04123-yUndifferentiated pleomorphic sarcomasMyxofibrosarcomasImmune microenvironmentMetastasis-free survivalRadiotherapy |
| spellingShingle | Siddh van Oost Debora M. Meijer Zeynep B. Erdem Marieke E. IJsselsteijn Jessica Roelands Suk Wai Lam Melissa S. Boejharat Brendy E. W. M. van den Akker Ruud van der Breggen Inge H. Briare-de Bruijn Lukas J. A. C. Hawinkels Anouk A. Kruiswijk Manon van der Ploeg Pauline M. Wijers-Koster Rick L. Haas Michiel A. J. van den Sande Noel F. C. C. de Miranda Judith V. M. G. Bovee Divergent therapeutic and prognostic impacts of immunogenic features in undifferentiated pleomorphic sarcoma and myxofibrosarcoma Cancer Immunology, Immunotherapy Undifferentiated pleomorphic sarcomas Myxofibrosarcomas Immune microenvironment Metastasis-free survival Radiotherapy |
| title | Divergent therapeutic and prognostic impacts of immunogenic features in undifferentiated pleomorphic sarcoma and myxofibrosarcoma |
| title_full | Divergent therapeutic and prognostic impacts of immunogenic features in undifferentiated pleomorphic sarcoma and myxofibrosarcoma |
| title_fullStr | Divergent therapeutic and prognostic impacts of immunogenic features in undifferentiated pleomorphic sarcoma and myxofibrosarcoma |
| title_full_unstemmed | Divergent therapeutic and prognostic impacts of immunogenic features in undifferentiated pleomorphic sarcoma and myxofibrosarcoma |
| title_short | Divergent therapeutic and prognostic impacts of immunogenic features in undifferentiated pleomorphic sarcoma and myxofibrosarcoma |
| title_sort | divergent therapeutic and prognostic impacts of immunogenic features in undifferentiated pleomorphic sarcoma and myxofibrosarcoma |
| topic | Undifferentiated pleomorphic sarcomas Myxofibrosarcomas Immune microenvironment Metastasis-free survival Radiotherapy |
| url | https://doi.org/10.1007/s00262-025-04123-y |
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