Undifferentiated pleomorphic sarcomas (UPS) represent a prevalent and aggressive subtype of soft tissue sarcomas (STS) in adults. Despite advancements in loco regional treatments, many patients with high grade STS, including UPS, develop metastatic disease. Neoadjuvant chemotherapy is a standard approach to mitigate this risk, but response variability necessitates refined patient selection strategies. This study investigated the correlation between UPS microenvironment and neoadjuvant chemotherapy response in resectable UPS. The NEOSARCOMICS study (NCT02789384) enrolled patients with resectable STS from six sarcoma centers in France. Patients received anthracycline based chemotherapy, followed by surgery. Histological response, gene expression profiling, and multiplex immunohistofluorescence were performed on baseline and post treatment tumor samples. Plasma proteomics was analyzed to identify biomarkers. Good responders to neoadjuvant chemotherapy showed enrichment in genes related to stemness and cell cycle regulation, while poor responders exhibited immune related gene enrichment. Proteomic profiling revealed immune pathway activation and downregulation of cell cycle pathways in non responders. Despite being associated with a good prognosis, high immune infiltration, particularly of CD8 + T cells and CD20 + B cells, predicts a poor response to neoadjuvant chemotherapy in UPS, suggesting the need for alternative therapeutic strategies for patients with inflamed UPS.Ongoing clinical trials are exploring the efficacy of combining chemotherapy with immune checkpoint inhibitors to improve outcomes.

中文翻译：

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肿瘤微环境对未分化多形性肉瘤患者新辅助化疗病理反应的预测价值


未分化多形性肉瘤 （UPS） 是成人软组织肉瘤 （STS） 的一种普遍且具有侵袭性的亚型。尽管局部区域治疗取得了进展，但许多高级别 STS（包括 UPS）患者会发展为转移性疾病。新辅助化疗是降低这种风险的标准方法，但反应的可变性需要改进的患者选择策略。本研究调查了可切除 UPS 微环境与新辅助化疗反应之间的相关性。NEOSARCOMICS 研究 （NCT02789384） 招募了来自法国 6 个肉瘤中心的可切除 STS 患者。患者接受基于蒽环类药物的化疗，然后进行手术。对基线和治疗后肿瘤样本进行组织学反应、基因表达谱和多重免疫组织荧光。分析血浆蛋白质组学以鉴定生物标志物。对新辅助化疗反应良好的患者表现出与干性和细胞周期调节相关的基因富集，而反应不佳的患者表现出免疫相关基因富集。蛋白质组学分析揭示了无反应者的免疫途径激活和细胞周期途径的下调。尽管预后良好，但高免疫浸润，尤其是 CD8 + T 细胞和 CD20 + B 细胞，预示着 UPS 对新辅助化疗的反应不佳，这表明炎症性 UPS 患者需要替代治疗策略。正在进行的临床试验正在探索化疗与免疫检查点抑制剂联合治疗以改善预后的疗效。