Wojas-Krawczyk Kamila, Krawczyk Paweł, Gil Michał, Strzemski Maciej
Pneumonology, Oncology and Allergology Department, Medical University of Lublin, 20-954 Lublin, Poland.
Genetics and Immunology Institute, GENIM Ltd., 20-609 Lublin, Poland.
Cancers (Basel). 2021 Jun 7;13(11):2836. doi: 10.3390/cancers13112836.
Due to the limited effectiveness of immunotherapy used as first-line monotherapy in patients with non-small-cell lung cancer (NSCLC), the concepts of combining classical immunotherapy based on immune checkpoint antibodies with other treatment methods have been developed. Pembrolizumab and atezolizumab were registered in combination with chemotherapy for the treatment of metastatic NSCLC, while durvalumab found its application in consolidation therapy after successful chemoradiotherapy in patients with locally advanced NSCLC. Exceptionally attractive, due to their relatively low toxicity and high effectiveness, are treatment approaches in which a combination of two different immunotherapy methods is applied. This method is based on observations from clinical trials in which nivolumab and ipilimumab were used as first-line therapy for advanced NSCLC. It turned out that the dual blockade of immune checkpoints activated T lymphocytes in different compartments of the immune response, at the same time affecting the downregulation of immune suppressor cells (regulatory T cells). These experiments not only resulted in the registration of combination therapy with nivolumab and ipilimumab, but also initiated other clinical trials using immune checkpoint inhibitors (ICIs) in combination with other ICIs or activators of costimulatory molecules found on immune cells. There are also studies in which ICIs are associated with molecules that modify the tumour environment. This paper describes the mechanism of the synergistic effect of a combination of different immunotherapy methods in NSCLC patients.
由于免疫疗法作为一线单药疗法用于非小细胞肺癌（NSCLC）患者的有效性有限，基于免疫检查点抗体的经典免疫疗法与其他治疗方法联合使用的概念应运而生。帕博利珠单抗和阿替利珠单抗已获批与化疗联合用于治疗转移性NSCLC，而度伐利尤单抗则用于局部晚期NSCLC患者放化疗成功后的巩固治疗。由于毒性相对较低且疗效较高，应用两种不同免疫疗法的联合治疗方法格外具有吸引力。该方法基于临床试验的观察结果，在这些试验中，纳武利尤单抗和伊匹木单抗被用作晚期NSCLC的一线治疗。结果表明，免疫检查点的双重阻断在免疫反应的不同区室中激活了T淋巴细胞，同时影响免疫抑制细胞（调节性T细胞）的下调。这些实验不仅促成了纳武利尤单抗和伊匹木单抗联合疗法的获批，还启动了其他临床试验，使用免疫检查点抑制剂（ICI）与其他ICI或免疫细胞上发现的共刺激分子激活剂联合使用。也有研究将ICI与改变肿瘤环境的分子联合使用。本文描述了不同免疫疗法联合在NSCLC患者中的协同作用机制。
