Divergent therapeutic and prognostic impacts of immunogenic features in undifferentiated pleomorphic sarcoma and myxofibrosarcoma.

IF 5.1
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
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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.

未分化多形性肉瘤和黏液纤维肉瘤免疫原性特征的不同治疗和预后影响。
未分化多形性肉瘤(UPS)和黏液纤维肉瘤(MFS)是具有不同形态特征的遗传复杂的软组织肉瘤。治疗通常包括手术,通常结合新辅助化疗或放疗。为了更好地了解这些肉瘤的免疫生物学及其与治疗反应和预后的关系,我们进行了转录组学和免疫表型分析。对13例UPS和10例MFS进行了RNA测序,并将免疫图谱与来自The Cancer Genome Atlas (n = 206,包括44例UPS和17例MFS)的软组织肉瘤数据进行了比较。使用成像细胞术进一步评估14例UPS和15例MFS的免疫状况。通过多光谱免疫荧光和免疫组织化学分析,进一步评估23例UPS和22例MFS患者肿瘤中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亚群表现出高T细胞浸润,而UPS与MFS相比表现出更高的骨髓细胞浸润。预后方面,T细胞和CD68+CD163+巨噬细胞与UPS的无转移生存相关,而与MFS无关。值得注意的是,在UPS中,新辅助放疗似乎诱导细胞毒性T细胞浸润和骨髓细胞耗损,而在MFS中没有观察到这些影响。这些发现突出了UPS和MFS在免疫生物学上的重要差异,具有治疗和预后意义。考虑到越来越多的免疫治疗选择用于治疗软组织肉瘤患者,这些差异应该被考虑在内。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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