Divergent therapeutic and prognostic impacts of immunogenic features in undifferentiated pleomorphic sarcoma and myxofibrosarcoma
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 sarco...
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| Published in: | Cancer Immunology, Immunotherapy : CII Vol. 74; no. 8; pp. 258 - 14 |
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| Main Authors: | , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Berlin/Heidelberg
Springer Berlin Heidelberg
02.07.2025
Springer Nature B.V Springer |
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| ISSN: | 1432-0851, 0340-7004, 1432-0851 |
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| 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. |
|---|---|
| AbstractList | 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. 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. 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. 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. 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.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. |
| ArticleNumber | 258 |
| Author | de Miranda, Noel F. C. C. Kruiswijk, Anouk A. Haas, Rick L. Erdem, Zeynep B. IJsselsteijn, Marieke E. van den Sande, Michiel A. J. van der Breggen, Ruud Roelands, Jessica Hawinkels, Lukas J. A. C. Meijer, Debora M. Wijers-Koster, Pauline M. Lam, Suk Wai van Oost, Siddh van den Akker, Brendy E. W. M. van der Ploeg, Manon Briare-de Bruijn, Inge H. Bovee, Judith V. M. G. Boejharat, Melissa S. |
| Author_xml | – sequence: 1 givenname: Siddh orcidid: 0000-0003-2281-5780 surname: van Oost fullname: van Oost, Siddh organization: Department of Pathology, Leiden University Medical Center, Leiden Center for Computational Oncology, LUMC – sequence: 2 givenname: Debora M. orcidid: 0000-0002-6399-3084 surname: Meijer fullname: Meijer, Debora M. organization: Department of Pathology, Leiden University Medical Center, Leiden Center for Computational Oncology, LUMC – sequence: 3 givenname: Zeynep B. orcidid: 0000-0002-0840-4689 surname: Erdem fullname: Erdem, Zeynep B. organization: Department of Pathology, Leiden University Medical Center, Leiden Center for Computational Oncology, LUMC – sequence: 4 givenname: Marieke E. orcidid: 0000-0002-8195-736X surname: IJsselsteijn fullname: IJsselsteijn, Marieke E. organization: Department of Pathology, Leiden University Medical Center – sequence: 5 givenname: Jessica orcidid: 0000-0003-3631-2041 surname: Roelands fullname: Roelands, Jessica organization: Department of Pathology, Leiden University Medical Center – sequence: 6 givenname: Suk Wai orcidid: 0000-0001-9782-5938 surname: Lam fullname: Lam, Suk Wai organization: Department of Pathology, Leiden University Medical Center – sequence: 7 givenname: Melissa S. surname: Boejharat fullname: Boejharat, Melissa S. organization: Department of Pathology, Leiden University Medical Center – sequence: 8 givenname: Brendy E. W. M. surname: van den Akker fullname: van den Akker, Brendy E. W. M. organization: Department of Pathology, Leiden University Medical Center – sequence: 9 givenname: Ruud orcidid: 0000-0003-2110-6069 surname: van der Breggen fullname: van der Breggen, Ruud organization: Department of Pathology, Leiden University Medical Center – sequence: 10 givenname: Inge H. orcidid: 0000-0002-9273-2828 surname: Briare-de Bruijn fullname: Briare-de Bruijn, Inge H. organization: Department of Pathology, Leiden University Medical Center – sequence: 11 givenname: Lukas J. A. C. orcidid: 0000-0002-2274-9325 surname: Hawinkels fullname: Hawinkels, Lukas J. A. C. organization: Department of Gastroenterology and Hepatology, Leiden University Medical Center – sequence: 12 givenname: Anouk A. orcidid: 0000-0003-4827-7466 surname: Kruiswijk fullname: Kruiswijk, Anouk A. organization: Department of Orthopedic Surgery, Leiden University Medical Center – sequence: 13 givenname: Manon orcidid: 0000-0001-7150-3068 surname: van der Ploeg fullname: van der Ploeg, Manon organization: Department of Pathology, Leiden University Medical Center – sequence: 14 givenname: Pauline M. orcidid: 0009-0002-4758-7016 surname: Wijers-Koster fullname: Wijers-Koster, Pauline M. organization: Department of Pathology, Leiden University Medical Center – sequence: 15 givenname: Rick L. orcidid: 0000-0003-4834-4331 surname: Haas fullname: Haas, Rick L. organization: Department of Radiotherapy, The Netherlands Cancer Institute, Department of Radiotherapy, Leiden University Medical Center – sequence: 16 givenname: Michiel A. J. orcidid: 0000-0002-9156-7656 surname: van den Sande fullname: van den Sande, Michiel A. J. organization: Department of Orthopedic Surgery, Leiden University Medical Center – sequence: 17 givenname: Noel F. C. C. orcidid: 0000-0001-6122-1024 surname: de Miranda fullname: de Miranda, Noel F. C. C. organization: Department of Pathology, Leiden University Medical Center, Leiden Center for Computational Oncology, LUMC – sequence: 18 givenname: Judith V. M. G. orcidid: 0000-0003-1155-0481 surname: Bovee fullname: Bovee, Judith V. M. G. email: J.V.M.G.Bovee@lumc.nl organization: Department of Pathology, Leiden University Medical Center, Leiden Center for Computational Oncology, LUMC |
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| Keywords | Immune microenvironment Radiotherapy Undifferentiated pleomorphic sarcomas Myxofibrosarcomas Metastasis-free survival |
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| PublicationTitle | Cancer Immunology, Immunotherapy : CII |
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| Snippet | Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are genetically complex soft tissue sarcomas with distinct morphological features.... Abstract Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are genetically complex soft tissue sarcomas with distinct morphological... |
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| SubjectTerms | Adult Aged Antibodies Antigens Biomarkers, Tumor - genetics Biopsy Cancer Research CD163 antigen Cytotoxicity Datasets Female Fibrosarcoma - genetics Fibrosarcoma - immunology Fibrosarcoma - mortality Fibrosarcoma - pathology Fibrosarcoma - therapy Gene expression Genomes Humans Immune microenvironment Immunofluorescence Immunogenicity Immunology Infiltration Lymphocytes T Lymphocytes, Tumor-Infiltrating - immunology Macrophages Macrophages - immunology Male Medicine Medicine & Public Health Metastases Metastasis-free survival Middle Aged Myeloid cells Myxofibrosarcomas Oncology Patients Prognosis Radiation therapy Radiotherapy Sarcoma Sarcoma - genetics Sarcoma - immunology Sarcoma - pathology Sarcoma - therapy Soft tissue sarcoma Transcriptomics Tumor Microenvironment - immunology Tumors Undifferentiated pleomorphic sarcomas |
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| Title | Divergent therapeutic and prognostic impacts of immunogenic features in undifferentiated pleomorphic sarcoma and myxofibrosarcoma |
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