靶向程序性细胞死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）免疫检查点的药物的可用性已经改变了晚期和/或转移性非小细胞肺癌（NSCLC）的治疗。然而，许多接受这些药物治疗的患者并不响应或只经历短暂的临床益处。即使在那些疾病有所反应的患者中，许多人随后也会经历疾病恶化。因此，需要新的方法来增强抗肿瘤免疫力并对PD-(L)1抑制剂的抗性进行反击，从而改善和/或延长PD-(L)1抑制剂敏感性和抑制剂耐药性NSCLC的患者反应和结果。在NSCLC中，导致对PD-(L)1抑制剂敏感性和/或抗性的机制包括其他免疫检查点的上调和/或免疫抑制性肿瘤微环境的存在，这些都是新疗法的潜在靶点。本文探讨了正在研究中的增强对PD-(L)1抑制剂反应和对抗抗性的新型治疗方案，并总结了NSCLC中的最新临床证据。© 2023 The Authors. Cancer（由Wiley Periodicals LLC代表美国癌症协会出版）

The availability of agents targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint has transformed treatment of advanced and/or metastatic non-small cell lung cancer (NSCLC). However, a substantial proportion of patients treated with these agents do not respond or experience only a brief period of clinical benefit. Even among those whose disease responds, many subsequently experience disease progression. Consequently, novel approaches are needed that enhance antitumor immunity and counter resistance to PD-(L)1 inhibitors, thereby improving and/or prolonging responses and patient outcomes, in both PD-(L)1 inhibitor-sensitive and inhibitor-resistant NSCLC. Mechanisms contributing to sensitivity and/or resistance to PD-(L)1 inhibitors in NSCLC include upregulation of other immune checkpoints and/or the presence of an immunosuppressive tumor microenvironment, which represent potential targets for new therapies. This review explores novel therapeutic regimens under investigation for enhancing responses to PD-(L)1 inhibitors and countering resistance, and summarizes the latest clinical evidence in NSCLC.© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.