Department of Respiratory Medicine, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.
Respir Investig. 2024 Mar;62(2):307-312. doi: 10.1016/j.resinv.2024.01.011. Epub 2024 Feb 3.
Immune checkpoint inhibitors (ICI) bind to programmed cell death-1 (PD-1)/PD-1 ligand-1 (PD-L1) and Cytotoxic T-lymphocyte antigen-4 (CTLA-4), which suppress T-cell function and inhibit their inhibitory function, resulting in T-cell activation. ICI have been approved for a wide range of cancers, including malignant melanoma, renal cell carcinoma, non-small cell lung cancer, head and neck cancer, Hodgkin's disease, small-cell lung cancer, malignant pleural mesothelioma, gastric cancer, esophageal cancer, breast cancer, uterine cancer, and hepatocellular carcinoma, and the number of indications continues to grow. In addition to the treatment of advanced disease, the anti-tumor effect has been demonstrated across disease stages, from locally advanced disease to early-stage operative disease. The treatment of lung cancer is at the forefront of this trend and long-term durable responses and survival benefits in lung cancer have been exhibited that were unimaginable when cytotoxic anticancer agents were the only treatment options. However, treatment efficacy varies greatly from case to case, and no biomarkers have been developed to accurately predict efficacy. In this article, we discuss the past and future of ICI therapy for lung cancer, based on clinical and basic evidence accumulated to-date.
免疫检查点抑制剂（ICI）与程序性细胞死亡-1（PD-1）/PD-1 配体-1（PD-L1）和细胞毒性 T 淋巴细胞相关抗原-4（CTLA-4）结合，抑制 T 细胞功能并抑制其抑制作用，导致 T 细胞激活。ICI 已被批准用于多种癌症，包括恶性黑色素瘤、肾细胞癌、非小细胞肺癌、头颈部癌、霍奇金淋巴瘤、小细胞肺癌、恶性胸膜间皮瘤、胃癌、食管癌、乳腺癌、子宫癌和肝细胞癌，适应证数量不断增加。除了治疗晚期疾病外，ICI 在疾病各阶段均显示出抗肿瘤作用，从局部晚期疾病到早期手术疾病。肺癌的治疗处于这一趋势的前沿，在肺癌中已经表现出了长期持久的缓解和生存获益，这在仅使用细胞毒性抗癌药物作为治疗选择时是不可想象的。然而，治疗效果因病例而异，目前尚未开发出生物标志物来准确预测疗效。本文基于迄今为止积累的临床和基础证据，讨论了 ICI 治疗肺癌的过去和未来。
