Division of Surgical Oncology, Department of Surgery, Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA.
Division of Medical Oncology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
Ann Surg Oncol. 2024 Mar;31(3):1865-1879. doi: 10.1245/s10434-023-14587-w. Epub 2023 Nov 21.
In the last decade, immunotherapy has become the cornerstone in the management of patients with melanoma, the foremost cause of skin-cancer-related death in the USA. The emergence of immune checkpoint blockade as a crucial element in current immunotherapy and combination strategies has significantly transformed the treatments of resectable and advanced (unresectable or metastatic) melanoma. This paper reviews the landmark clinical trials that formed the basis of management of melanoma in the perioperative and metastatic setting. Furthermore, we discuss the rationale for the applications of PD-1 blockade and its combination with anti-CTLA-4 and anti-LAG-3. The review also explores new experimental combinations of PD-1 blockade with other immunomodulatory agents, including targeted therapies, anti-TIGIT antibodies, TLR-9 agonists, antiangiogenic agents, and mRNA vaccines.
在过去的十年中，免疫疗法已成为美国皮肤癌相关死亡首要原因——黑色素瘤患者治疗的基石。免疫检查点阻断作为当前免疫疗法和联合策略中的关键要素的出现，极大地改变了可切除和晚期（不可切除或转移）黑色素瘤的治疗方法。本文回顾了形成可切除和转移性黑色素瘤围手术期和转移期管理基础的具有里程碑意义的临床试验。此外，我们还讨论了 PD-1 阻断及其与抗 CTLA-4 和抗 LAG-3 的联合应用的原理。该综述还探讨了 PD-1 阻断与其他免疫调节药物（包括靶向治疗、抗 TIGIT 抗体、TLR-9 激动剂、抗血管生成药物和 mRNA 疫苗）的新实验性联合应用。
