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
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Leiden Center for Computational Oncology, LUMC, Leiden, The Netherlands.
Cancer Immunol Immunother. 2025 Jul 2;74(8):258. doi: 10.1007/s00262-025-04123-y.
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 CD68CD163 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.
未分化多形性肉瘤（UPS）和黏液纤维肉瘤（MFS）是具有独特形态特征的基因复杂的软组织肉瘤。治疗通常包括手术，常联合新辅助化疗或放疗。为了更好地理解这些肉瘤的免疫生物学及其与治疗反应和预后的关系，我们进行了转录组和免疫表型分析。对13例UPS和10例MFS进行了RNA测序，并将免疫谱与来自癌症基因组图谱的软组织肉瘤数据（n = 206，包括44例UPS和17例MFS）进行了比较。使用成像质谱流式细胞术在14例UPS和15例MFS中进一步评估免疫微环境。通过多光谱免疫荧光和免疫组织化学分析，在23例UPS和22例MFS中进一步评估肿瘤中T细胞和巨噬细胞浸润的特征。与其他软组织肉瘤相比，UPS和MFS表现出免疫原性特征，UPS和MFS的亚组表现出高T细胞浸润，而与MFS相比，UPS表现出更高的髓样细胞浸润。在预后方面，T细胞和CD68CD163巨噬细胞与UPS的无转移生存期相关，但与MFS无关。值得注意的是，在UPS中，新辅助放疗似乎诱导了细胞毒性T细胞浸润和髓样细胞耗竭，而在MFS中未观察到这些效应。这些发现突出了UPS和MFS免疫生物学的重要差异，具有治疗和预后意义。鉴于治疗软组织肉瘤患者的免疫治疗选择越来越多，应考虑这些差异。
