Pakkala Suchita, Owonikoko Taofeek K
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.
J Thorac Dis. 2018 Feb;10(Suppl 3):S460-S467. doi: 10.21037/jtd.2017.12.51.
Small cell lung cancer (SCLC) is a rapidly progressive cancer that often debilitates patients within months of detection and quickly becomes refractory to the limited options of therapy. While SCLC is not generally considered an immunogenic tumor, clinical experience suggests that patients with robust immune response manifesting as paraneoplastic syndrome are more likely to present with limited stage of the disease and tend to have a better prognosis. Monoclonal antibodies targeting critical negative regulators of immune response, so called immune checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) have expanded the application of immune-based therapies to increasing number of advanced stage cancers. These agents overcome the inhibitory immune signals leading to a heightened immune response against cancer cells. These immune checkpoint inhibitors have established efficacy leading to regulatory approval for their use in many cancer types including non-small cell lung cancer (NSCLC). Evaluation of the CTLA-4 inhibitor, ipilimumab and PD-1 inhibitors, nivolumab and pembrolizumab in SCLC have shown encouraging signal but definitive studies are still ongoing. In this review, we discuss the rationale behind the use of checkpoint inhibitors in SCLC, contextualize the results of early trials of immunotherapy agents in SCLC and project the future evolution of this strategy.
小细胞肺癌（SCLC）是一种进展迅速的癌症，常常在被发现后的数月内使患者身体衰弱，并且很快就会对有限的治疗选择产生耐药性。虽然SCLC通常不被认为是一种免疫原性肿瘤，但临床经验表明，表现为副肿瘤综合征的具有强大免疫反应的患者更有可能表现为疾病的局限期，并且往往预后较好。靶向免疫反应关键负调节因子（即所谓的免疫检查点）的单克隆抗体，如细胞毒性T淋巴细胞相关蛋白4（CTLA-4）和程序性死亡1（PD-1），已经将基于免疫的疗法应用于越来越多的晚期癌症。这些药物克服了抑制性免疫信号，从而增强了针对癌细胞的免疫反应。这些免疫检查点抑制剂已经确立了疗效，并因此获得监管批准用于包括非小细胞肺癌（NSCLC）在内的多种癌症类型。对CTLA-4抑制剂伊匹单抗以及PD-1抑制剂纳武单抗和派姆单抗在SCLC中的评估已显示出令人鼓舞的信号，但确定性研究仍在进行中。在本综述中，我们讨论了在SCLC中使用检查点抑制剂的基本原理，将免疫治疗药物在SCLC中的早期试验结果置于背景中，并预测该策略的未来发展。
