Abstract:
Soft tissue sarcoma is a rare and aggressive disease with a 40 to 50% metastasis rate. The limited efficacy of traditional approaches with surgery, radiation, and chemotherapy has prompted research in novel immunotherapy for soft tissue sarcoma. Immune checkpoint inhibitors such as anti-CTLA-4 and PD-1 therapies in STS have demonstrated histologic-specific responses. Some combinations of immunotherapy with chemotherapy, TKI, and radiation were effective. STS is considered a \'cold\', non-inflamed tumor. Adoptive cell therapies are actively investigated in STS to enhance immune response. Genetically modified T-cell receptor therapy targeting cancer testis antigens such as NY-ESO-1 and MAGE-A4 demonstrated durable responses, especially in synovial sarcoma. Two early HER2-CAR T-cell trials have achieved stable disease in some patients. In the future, CAR-T cell therapies will find more specific targets in STS with a reliable response. Early recognition of T-cell induced cytokine release syndrome is crucial, which can be alleviated by immunosuppression such as steroids. Further understanding of the immune subtypes and biomarkers will promote the advancement of soft tissue sarcoma treatment.
摘要:
软组织肉瘤是一种罕见且侵袭性的疾病,转移率为40%至50%。传统手术方法的疗效有限,辐射,化疗促进了软组织肉瘤新型免疫治疗的研究。STS中的免疫检查点抑制剂如抗CTLA-4和PD-1疗法已显示出组织学特异性反应。免疫疗法和化疗的一些组合,TKI,辐射是有效的。STS被认为是“冷”,非发炎肿瘤.在STS中积极研究过继细胞疗法以增强免疫应答。针对肿瘤睾丸抗原如NY-ESO-1和MAGE-A4的基因修饰T细胞受体治疗表现出持久的反应。尤其是滑膜肉瘤.两项早期HER2-CAR-T细胞试验已经在一些患者中实现了稳定的疾病。在未来,CAR-T细胞疗法将在STS中找到更具体的靶标,并具有可靠的反应。早期识别T细胞诱导的细胞因子释放综合征至关重要,可以通过类固醇等免疫抑制来缓解。对免疫亚型和生物标志物的进一步了解将促进软组织肉瘤治疗的发展。