非小细胞肺癌(NSCLC)已经成为精准医学的典范，大量特定的致癌驱动基因突变的疾病亚型被发现，导致了一系列分子靶向治疗的发展。在过去的十年中，针对NSCLC的免疫检查点抑制剂(ICIs)的开发也取得了快速进展，特别是对PD-L1-PD-1轴的拮抗抗体的开发，用于NSCLC的治疗。尽管NSCLC的许多主要致癌驱动基因与ICIs的固有耐药性相关，但某些致癌基因驱动子型的患者，这些子型高度响应特定的靶向治疗，也可能从免疫治疗中获益。然而，发展针对致癌基因成瘾性NSCLC的有效免疫治疗方法，面临着患者选择的缺失预测生物标记以及ICIs和致癌驱动靶向治疗如何组合的知识的限制。因此，在特定致癌驱动基因突变的选定条件下，ICIs单独使用还是与化疗联合使用甚至与分子靶向药物联合使用，是否提供与未选定NSCLC人群相似的益处，仍然是一个悬而未决的问题。在本综述中，我们讨论致癌驱动突变对ICIs疗效和免疫肿瘤微环境的影响，以及可以利用的潜在弱点，以克服致癌基因成瘾性NSCLC免疫疗法的挑战。 © 2023. Springer Nature Limited.

Non-small-cell lung cancer (NSCLC) has become a paradigm of precision medicine, with the discovery of numerous disease subtypes defined by specific oncogenic driver mutations leading to the development of a range of molecularly targeted therapies. Over the past decade, rapid progress has also been made in the development of immune-checkpoint inhibitors (ICIs), especially antagonistic antibodies targeting the PD-L1-PD-1 axis, for the treatment of NSCLC. Although many of the major oncogenic drivers of NSCLC are associated with intrinsic resistance to ICIs, patients with certain oncogene-driven subtypes of the disease that are highly responsive to specific targeted therapies might also derive benefit from immunotherapy. However, the development of effective immunotherapy approaches for oncogene-addicted NSCLC has been challenged by a lack of predictive biomarkers for patient selection and limited knowledge of how ICIs and oncogene-directed targeted therapies should be combined. Therefore, whether ICIs alone or with chemotherapy or even in combination with molecularly targeted agents would offer comparable benefit in the context of selected oncogenic driver alterations to that observed in the general unselected NSCLC population remains an open question. In this Review, we discuss the effects of oncogenic driver mutations on the efficacy of ICIs and the immune tumour microenvironment as well as the potential vulnerabilities that could be exploited to overcome the challenges of immunotherapy for oncogene-addicted NSCLC.© 2023. Springer Nature Limited.