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
Main Authors: 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.
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 02.07.2025
Springer Nature B.V
Springer
Subjects:
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
Online Access:Get full text
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Summary: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.
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ISSN:1432-0851
0340-7004
1432-0851
DOI:10.1007/s00262-025-04123-y