Kwok Hoi-Hin, Yang Jiashuang, Lam David Chi-Leung
Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Cancers (Basel). 2023 May 13;15(10):2749. doi: 10.3390/cancers15102749.
The rapid development of targeted therapy paved the way toward personalized medicine for advanced non-small cell lung cancer (NSCLC). Lung adenocarcinoma (ADC) harboring actionable genetic alternations including epidermal growth factor receptor (), anaplastic lymphoma kinase (), Kirsten rat sarcoma virus () and c-ros oncogene 1 () treated with tyrosine kinase inhibitors (TKIs) incurred lesser treatment toxicity but better therapeutic responses compared with systemic chemotherapy. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) have also shown an increase in overall survival (OS) for NSCLC patients. However, acquired resistance to these targeted therapies remains a major obstacle to long-term maintenance treatment for lung ADC patients. The emergence of immune checkpoint inhibitors (ICIs) against programmed cell death protein 1 (PD-1) or programmed cell death-ligand 1 (PD-L1) has changed the treatment paradigm for NSCLC tumors without actionable genetic alternations. Clinical studies have suggested, however, that there are no survival benefits with the combination of targeted therapy and ICIs. In this review, we will summarize and discuss the current knowledge on the tumor immune microenvironment and the dynamics of immune phenotypes, which could be crucial in extending the applicability of ICIs for this subpopulation of lung ADC patients.
靶向治疗的迅速发展为晚期非小细胞肺癌（NSCLC）的个性化医疗铺平了道路。携带可靶向治疗的基因改变的肺腺癌（ADC），包括表皮生长因子受体（EGFR）、间变性淋巴瘤激酶（ALK）、 Kirsten大鼠肉瘤病毒（KRAS）和c-ros癌基因1（ROS1），与全身化疗相比，用酪氨酸激酶抑制剂（TKIs）治疗时毒性较小，但治疗反应更好。针对血管内皮生长因子（VEGF）的血管生成抑制剂也显示可提高NSCLC患者的总生存期（OS）。然而，对这些靶向治疗产生获得性耐药仍然是肺ADC患者长期维持治疗的主要障碍。针对程序性细胞死亡蛋白1（PD-1）或程序性细胞死亡配体1（PD-L1）的免疫检查点抑制剂（ICIs）的出现改变了无可靶向治疗基因改变的NSCLC肿瘤的治疗模式。然而，临床研究表明，靶向治疗与ICIs联合使用并无生存获益。在本综述中，我们将总结并讨论关于肿瘤免疫微环境和免疫表型动态变化的当前知识，这对于扩大ICIs在这一亚组肺ADC患者中的应用可能至关重要。
