软组织肉瘤(STS)是起源于间充质组织的恶性肿瘤。进展性和转移性的STS患者有低的总生存率和相对有限的治疗选择。OnCostatin M (OSM)是一种多效性细胞因子，被证明在各种癌症类型中具有促进和抗肿瘤性。然而，OSM在STS中的作用尚未阐明。此外，OSM和抗PD-1疗法的潜在附加效应迄今尚未进行。本研究旨在确定体外给予OSM对于脂肪肉瘤、平滑肌肉瘤和粘液纤维肉瘤免疫细胞的影响以及OSM和尼伯露铂在治疗这些STS中的潜在合作性质。我们设计了一项队列研究，探索目标STS中的新型组织学驱动的治疗方法。从STS患者的外周血和肿瘤中分离出免疫细胞，与治疗性单克隆抗体培养后，通过流式细胞术评估免疫细胞的比例和表型。OSM未影响外周CD45+细胞的比例，但nivolumab显著增加了外周CD45+细胞的比例，而两种治疗均对CD8+ T细胞产生影响。在肿瘤组织中，nivolumab提高了CD8+ T细胞和CD45‒ TRAIL+细胞培养，而OSM显著丰富了CD8+ T细胞和CD45‒ TRAIL+细胞培养。我们的数据表明，OSM可能在平滑肌肉瘤、粘液纤维肉瘤和脂肪肉瘤的治疗中发挥作用。总的来说，OSM的生物效力主要体现在我们队列的肿瘤微环境中，而不是患者的外周血液中，nivolumab可以在选定的病例中增强其作用机制。然而，还需要更多的组织类型定制的研究，以充分理解OSM在STS中的功能。©2023作者。S. Karger AG，巴塞尔出版。

Soft tissue sarcomas (STSs) are malignant tumors arising from mesenchymal tissues. Patients with advanced and metastatic STSs have low overall survival rates and relatively limited treatment options. Oncostatin M (OSM) is a pleiotropic cytokine that was shown to carry both pro- and anti-tumorigenic properties in various cancer types. However, the role of OSM in STSs has not yet been elucidated. Moreover, the potential additive effects of combining OSM and anti-PD-1 therapy have not been carried out so far.The aim of this study was to determine the effects of in vitro OSM administration on liposarcoma, leiomyosarcoma, and myxofibrosarcoma immune cells isolated from peripheral blood and tumor tissues and the potential cooperative nature of OSM and nivolumab in treating these STSs. We designed a cohort study to explore novel histology-driven therapies in our target STSs. The immune cells were isolated from the peripheral blood and tumors of patients with STS, and the proportions and phenotypes of immune cells were evaluated with flow cytometry after cultivation with therapeutic monoclonal antibodies.The proportion of peripheral CD45+ cells was not affected by OSM but was significantly increased by nivolumab, whereas both treatments had an effect on CD8+ T cells. In tumor tissues, CD8+ T cell and CD45‒ TRAIL+ cell cultures were boosted by nivolumab and significantly enriched by OSM. Our data suggest that OSM may play a role in the treatment of leiomyosarcoma, myxofibrosarcoma, and liposarcoma.In conclusion, the biological efficacy of OSM is reflected in the tumor microenvironment rather than in the peripheral blood of the patients in our cohort, and nivolumab could potentiate its mechanism of action in selected cases. Nevertheless, more histotype-tailored studies are needed to fully understand the functions of OSM in STSs.© 2023 The Author(s). Published by S. Karger AG, Basel.