Columbia University Medical Center, 177 Fort Washington Avenue, MHB 6GN-435, New York, NY 10032, United States.
Columbia University Medical Center, 177 Fort Washington Avenue, MHB 6GN-435, New York, NY 10032, United States.
Pharmacol Ther. 2018 Jun;186:130-137. doi: 10.1016/j.pharmthera.2018.01.003. Epub 2018 Jan 31.
Antitumor immunity relies on the ability of the immune system to recognize tumor cells as foreign and eliminate them. An effective immune response in this setting is due to surveillance of tumor-specific antigens that induce an adaptive immune response resulting in T-cell mediated cytotoxicity. Immune checkpoint inhibitors, specifically those targeting the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis, have demonstrated promising activity in non-small cell lung cancer (NSCLC). However, there remains a crucial need for better treatment strategies for the majority of patients with advanced NSCLC, particularly in the frontline setting. Chemotherapy can increase antigenicity via immunogenic cell death (ICD) of tumor cells as well as also reduce "off target" immunosuppression in the tumor microenvironment (TME). Combining chemotherapy with PD-1 blockade harnesses the potential synergy between these agents and has led to encouraging results in the up-front treatment of NSCLC. In this review, we summarize the preclinical rationale behind these combinations and review recent trial data demonstrating their efficacy.
抗肿瘤免疫依赖于免疫系统识别肿瘤细胞为外来并将其消除的能力。在这种情况下，有效的免疫反应是由于对肿瘤特异性抗原的监测，这些抗原诱导适应性免疫反应，导致 T 细胞介导的细胞毒性。免疫检查点抑制剂，特别是针对程序性细胞死亡蛋白 1（PD-1）/程序性细胞死亡配体 1（PD-L1）轴的抑制剂，在非小细胞肺癌（NSCLC）中显示出有前途的活性。然而，对于大多数晚期 NSCLC 患者，特别是在一线治疗中，仍然迫切需要更好的治疗策略。化疗可以通过肿瘤细胞的免疫原性细胞死亡（ICD）增加抗原性，同时还可以减少肿瘤微环境（TME）中的“脱靶”免疫抑制作用。将化疗与 PD-1 阻断联合使用，可以利用这些药物之间的潜在协同作用，并在前瞻性治疗 NSCLC 中取得令人鼓舞的结果。在这篇综述中，我们总结了这些联合治疗背后的临床前原理，并回顾了最近的临床试验数据，证明了它们的疗效。
