Supplementary Material for: Long-Term Remission with Ipilimumab/Nivolumab in Two Patients with Different Soft Tissue Sarcoma Subtypes and No PD-L1 Expression

Checkpoint inhibitor therapy has been shown to improve outcomes in multiple solid malignancies; however, data are limited in soft tissue sarcoma. We present two cases of patients with advanced soft tissue sarcoma of different subtypes (dedifferentiated liposarcoma and myxofibrosarcoma) with zero percent PD-L1 expression by immunohistochemistry who were treated with ipilimumab and nivolumab followed by maintenance nivolumab. Both patients had failed multiple lines of systemic treatment and experienced long-term remission after starting ipilimumab and nivolumab. Genetic testing revealed that no genetic mutations were found in common between the two cases. One patient received concurrent cryoablation, which may have sensitized his tumor to immunotherapy. Checkpoint inhibitor therapy may improve outcomes in soft tissue sarcoma regardless of PD-L1 status, especially when combined with cryoablation. Studies are needed to evaluate whether treatment response varies by sarcoma subtype and what molecular markers can be used to guide patient selection.

免疫检查点抑制剂疗法（checkpoint inhibitor therapy）已被证实可改善多种实体恶性肿瘤的预后，但目前软组织肉瘤领域的相关临床数据仍较为有限。本研究报告2例不同亚型晚期软组织肉瘤患者的病例：1例为去分化脂肪肉瘤（dedifferentiated liposarcoma），另1例为黏液纤维肉瘤（myxofibrosarcoma），二者经免疫组织化学（immunohistochemistry）检测均呈0%的程序性死亡配体1（Programmed Death-Ligand 1，PD-L1）表达；两名患者均已接受过多线系统性治疗且治疗失败，在接受伊匹木单抗（ipilimumab）联合纳武利尤单抗（nivolumab）治疗并后续予以纳武利尤单抗维持治疗后，均获得了长期缓解。基因检测结果显示，两例患者未检出共同存在的基因突变。其中1例患者同步接受了冷冻消融术（cryoablation）治疗，该治疗或可使其肿瘤对免疫检查点抑制剂疗法更为敏感。本研究提示，无论PD-L1表达状态如何，免疫检查点抑制剂疗法或均可改善软组织肉瘤患者的预后，尤其是与冷冻消融术联合应用时。未来仍需开展相关研究，以明确不同肉瘤亚型对治疗的应答是否存在差异，以及可用于指导患者筛选的分子标志物。