Gomatou Georgia, Charpidou Andriani, Li Peifeng, Syrigos Nikolaos, Gkiozos Ioannis
Oncology Unit, Third Department of Medicine, "Sotiria" General Hospital for Chest Diseases, National and Kapodistrian University of Athens, Athens, Greece.
Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Clin Transl Oncol. 2025 Apr;27(4):1426-1437. doi: 10.1007/s12094-024-03731-x. Epub 2024 Sep 22.
Immune checkpoint inhibitors (ICIs) redefined the therapeutics of non-small cell lung cancer (NSCLC), leading to significant survival benefits and unprecedented durable responses. However, the majority of the patients develop resistance to ICIs, either primary or acquired. Establishing a definition of primary resistance to ICIs in different clinical scenarios is challenging and remains a work in progress due to the changing landscape of ICI-based regimens, mainly in the setting of early-stage NSCLC. The mechanisms of primary resistance to ICIs in patients with NSCLC include a plethora of pathways involving a cross-talk of the tumor cells, the tumor microenvironment and the host, leading to the development of an immunosuppressive phenotype. The optimal management of patients with NSCLC following primary resistance to ICIs represents a significant challenge in current thoracic oncology. Research in this field includes exploring other immunotherapeutic approaches, such as cancer vaccines, and investigating novel antibody-drug conjugates in patients with NSCLC.
免疫检查点抑制剂（ICI）重新定义了非小细胞肺癌（NSCLC）的治疗方法，带来了显著的生存获益和前所未有的持久反应。然而，大多数患者会对ICI产生耐药性，包括原发性耐药和获得性耐药。由于基于ICI的治疗方案不断变化，主要是在早期NSCLC的情况下，在不同临床场景中建立原发性ICI耐药的定义具有挑战性，仍在不断完善中。NSCLC患者对ICI原发性耐药的机制包括大量涉及肿瘤细胞、肿瘤微环境和宿主相互作用的途径，导致免疫抑制表型的形成。在原发性ICI耐药后，NSCLC患者的最佳管理是当前胸部肿瘤学中的一项重大挑战。该领域的研究包括探索其他免疫治疗方法，如癌症疫苗，以及研究NSCLC患者的新型抗体药物偶联物。
