Schmid Sabine, Früh Martin
Department of Oncology, Haematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
J Thorac Dis. 2018 May;10(Suppl 13):S1503-S1508. doi: 10.21037/jtd.2018.01.113.
Despite extensive research no meaningful progress in systemic treatment of small cell lung cancer (SCLC) has been made in the past decades. Earlier attempts with immunotherapy including interferon and vaccination approaches had limited success. High mutational load, smoking history and potentially also the frequent presence of paraneoplastic phenomena-indicating an activated immune system-represent a rationale for a benefit from immune checkpoint inhibitors in SCLC. However, the likelihood of response is diminished due to poor T-cell activation resulting from low expression of MHC class I antigens, low amounts of tumor infiltrating lymphocytes (TILs) and low PD-L1 expression rates. Recently, early reports from studies with checkpoint inhibitors have shown promising results with the potential for long term disease control in a subset of SCLC patients. However, reliable predictive biomarkers to better define the population drawing most benefit are currently lacking. Results from ongoing phase III trials in different treatment lines and in the maintenance setting are eagerly awaited.
尽管进行了广泛的研究，但在过去几十年里，小细胞肺癌（SCLC）的系统治疗并未取得有意义的进展。早期的免疫治疗尝试，包括干扰素和疫苗接种方法，取得的成功有限。高突变负荷、吸烟史以及可能频繁出现的副肿瘤现象（表明免疫系统激活）为小细胞肺癌患者从免疫检查点抑制剂中获益提供了理论依据。然而，由于MHC I类抗原表达低、肿瘤浸润淋巴细胞（TILs）数量少以及PD-L1表达率低导致T细胞激活不良，应答的可能性降低。最近，关于检查点抑制剂研究的早期报告显示了有希望的结果，在一部分小细胞肺癌患者中具有长期疾病控制的潜力。然而，目前缺乏可靠的预测生物标志物来更好地确定最能获益的人群。人们急切期待正在进行的不同治疗线和维持治疗阶段III期试验的结果。
