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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Vydané v:	Cancer Immunology, Immunotherapy : CII Ročník 74; číslo 8; s. 258 - 14
Hlavní autori:	van Oost, Siddh, Meijer, Debora M., Erdem, Zeynep B., IJsselsteijn, Marieke E., Roelands, Jessica, Lam, Suk Wai, Boejharat, Melissa S., van den Akker, Brendy E. W. M., van der Breggen, Ruud, Briare-de Bruijn, Inge H., Hawinkels, Lukas J. A. C., Kruiswijk, Anouk A., van der Ploeg, Manon, Wijers-Koster, Pauline M., Haas, Rick L., van den Sande, Michiel A. J., de Miranda, Noel F. C. C., Bovee, Judith V. M. G.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Berlin/Heidelberg Springer Berlin Heidelberg 02.07.2025 Springer Nature B.V Springer
Predmet:	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 Netherlands Immune microenvironment Radiotherapy Undifferentiated pleomorphic sarcomas Myxofibrosarcomas Metastasis-free survival
ISSN:	1432-0851, 0340-7004, 1432-0851
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1432-0851 0340-7004 1432-0851
DOI:	10.1007/s00262-025-04123-y