免疫疗法在软组织肉瘤治疗中的作用:现状与展望。
The Role of Immunotherapy in the Management of Soft Tissue Sarcomas: Current Landscape and Future Outlook.
机构信息
1Memorial Sloan Kettering Cancer Center, New York, New York.
出版信息
J Natl Compr Canc Netw. 2022 Jul;20(7):834-844. doi: 10.6004/jnccn.2022.7027.
Soft tissue sarcomas (STS) are a subset of sarcoma, a rare group of heterogeneous malignancies of mesenchymal origin. Current standard of care involves surgical resection with systemic chemotherapy used to treat high-risk localized and metastatic disease. Though classically thought to be immunologically quiet tumors, STS interact with the immune system, undergoing immunoediting that alters tumor immunogenicity and the tumor microenvironment. Recent advances with immune checkpoint inhibition have led to clinical trials exploring the efficacy of immunotherapy in treating STS. Results from these trials point to histologic subtype-specific clinical activity of immune checkpoint blockade. In addition, combinatorial strategies adding immune checkpoint inhibition to local or systemic therapies for STS have further increased their efficacy. Targeted immunotherapies using engineered T-cell receptor-based approaches also show increasing promise as treatment options for some patients with STS. Adoptive transfer of autologous T cells targeting NY-ESO-1 and MAGE-A4 have high response rates in sarcomas expressing these antigens, although recurrence is often seen in responding patients. Future work must focus on identifying primary and acquired mechanisms of resistance to these therapies, and extend T-cell receptor discovery to other tumor-associated antigens.
软组织肉瘤(STS)是肉瘤的一个亚组,是一种罕见的源自间充质的异质性恶性肿瘤。目前的标准治疗方法包括手术切除和全身化疗,用于治疗高危局限性和转移性疾病。尽管 STS 通常被认为是免疫沉默的肿瘤,但它们与免疫系统相互作用,经历免疫编辑,改变肿瘤的免疫原性和肿瘤微环境。免疫检查点抑制的最新进展导致了临床试验,探索免疫疗法治疗 STS 的疗效。这些试验的结果表明,免疫检查点阻断具有组织亚型特异性的临床活性。此外,将免疫检查点抑制与 STS 的局部或全身治疗相结合的联合策略进一步提高了其疗效。使用基于工程化 T 细胞受体的靶向免疫疗法也为一些 STS 患者提供了越来越有希望的治疗选择。针对表达这些抗原的肉瘤,靶向 NY-ESO-1 和 MAGE-A4 的自体 T 细胞过继转移具有很高的反应率,但在有反应的患者中经常出现复发。未来的工作必须集中于确定对这些治疗方法的原发性和获得性耐药机制,并将 T 细胞受体的发现扩展到其他肿瘤相关抗原。