Medical Oncology Department, Hospital General Universitario Gregorio Marañon, Calle del Doctor Esquerdo, 46, 28007, Madrid, Spain.
Instituto de Investigacion Sanitaria Gregorio Marañon, Madrid, Spain.
Clin Transl Oncol. 2019 Aug;21(8):961-976. doi: 10.1007/s12094-018-02011-9. Epub 2019 Jan 12.
Despite decades of research, prognosis for SCLC patients remains poor, and treatment options limited. SCLC is an immunogenic tumor with high somatic mutation rates due to tobacco exposure resulting in potential neo-antigens, the presence of suppressed immune responses, and occurrence of paraneoplastic disorders. The use of T cell immune-checkpoint inhibitors (anti-PD1: nivolumab, pembrolizumab; anti-PD-L1: atezolizumab, durvalumab; anti-CTLA-4: ipilimumab, tremelimumab) have shown promising antitumor activity with the potential to prolong survival in SCLC patients. In fact, atezolizumab when combined with chemotherapy has achieved the milestone of being the first drug to improve survival in patients with newly diagnosed extensive-stage SCLC. Other immunotherapeutic approaches evaluated in clinical trials for SCLC include the use of cytokines, cancer vaccines, antiganglioside therapies, TLR9 inhibition, anti-Notch signaling, and anti-CD47. This review discusses the rationale and clinical evidence of immunotherapy in SCLC, the conflictive clinical results of novel immunotherapeutic agents and combinatorial therapies under evaluation in SCLC patients.
尽管经过了几十年的研究，小细胞肺癌患者的预后仍然很差，治疗选择也很有限。小细胞肺癌是一种免疫原性肿瘤，由于暴露于烟草而导致体细胞突变率高，从而产生潜在的新抗原，存在受抑制的免疫反应，并且发生副肿瘤性疾病。免疫检查点抑制剂（抗 PD-1：nivolumab、pembrolizumab；抗 PD-L1：atezolizumab、durvalumab；抗 CTLA-4：ipilimumab、tremelimumab）的使用已显示出有希望的抗肿瘤活性，有可能延长小细胞肺癌患者的生存时间。事实上，atezolizumab 与化疗联合使用已取得里程碑式的成就，成为首个能够改善广泛期小细胞肺癌患者生存的药物。在临床试验中评估的其他免疫治疗方法包括使用细胞因子、癌症疫苗、抗神经节苷脂疗法、TLR9 抑制、抗 Notch 信号传导和抗 CD47。这篇综述讨论了免疫疗法在小细胞肺癌中的原理和临床证据，以及在小细胞肺癌患者中评估的新型免疫治疗药物和联合疗法的有冲突的临床结果。
