软组织肉瘤是侵袭性间质来源的恶性肿瘤。未分化多形性肉瘤（UPS）属于侵袭性、高级且特征最少的肉瘤亚型，影响多个组织并转移至多个器官。局部 UPS 的治疗包括手术结合放射治疗。转移性形式采用化疗治疗。免疫疗法是许多癌症的一种有前途的治疗方式。然而，由于其异质性、抗原景观变异、免疫细胞浸润较低以及用于临床前研究的已建立的患者来源的 UPS 细胞系数量有限，UPS 免疫疗法的发展受到限制。在这项研究中，我们建立并表征了一种新型患者来源的 UPS 细胞系 JBT19。 JBT19 细胞表达 PD-L1 和胶原蛋白（免疫检查点分子 LAIR-1 的配体）。 JBT19细胞可以在体外形成球状体，并在免疫缺陷裸鼠中形成实体瘤。我们发现 JBT19 细胞诱导 JBT19 反应性自体和同种异体 NK、T 和 NKT 样细胞的扩增，并且扩增细胞的反应性与对 JBT19 细胞的细胞毒性影响相关。表达 PD-1 和 LAIR-1 配体的 JBT19 细胞显示出离体免疫原性和有效的体内异种移植特性，可以为临床前研究提供独特的资源，开发治疗 UPS 的新型免疫治疗干预措施。© 2023。 ）。

Soft tissue sarcomas are aggressive mesenchymal-origin malignancies. Undifferentiated pleomorphic sarcoma (UPS) belongs to the aggressive, high-grade, and least characterized sarcoma subtype, affecting multiple tissues and metastasizing to many organs. The treatment of localized UPS includes surgery in combination with radiation therapy. Metastatic forms are treated with chemotherapy. Immunotherapy is a promising treatment modality for many cancers. However, the development of immunotherapy for UPS is limited due to its heterogeneity, antigenic landscape variation, lower infiltration with immune cells, and a limited number of established patient-derived UPS cell lines for preclinical research. In this study, we established and characterized a novel patient-derived UPS cell line, JBT19. The JBT19 cells express PD-L1 and collagen, a ligand of the immune checkpoint molecule LAIR-1. JBT19 cells can form spheroids in vitro and solid tumors in immunodeficient nude mice. We found JBT19 cells induce expansion of JBT19-reactive autologous and allogeneic NK, T, and NKT-like cells, and the reactivity of the expanded cells was associated with cytotoxic impact on JBT19 cells. The PD-1 and LAIR-1 ligand-expressing JBT19 cells show ex vivo immunogenicity and effective in vivo xenoengraftment properties that can offer a unique resource in the preclinical research developing novel immunotherapeutic interventions in the treatment of UPS.© 2023. The Author(s).