Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Department of Thoracic Medical Oncology, Hunan Cancer Hospital/the affiliated Cancer Hospital of Xiangya school of Medicine, Central South University, 283 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, China.
BMC Cancer. 2018 Nov 8;18(1):1082. doi: 10.1186/s12885-018-4990-5.
Recent breakthroughs in targeted therapy and immunotherapy have revolutionized the treatment of lung cancer, the leading cause of cancer-related deaths in the United States and worldwide. Here we provide an overview of recent progress in immune checkpoint blockade therapy for treatment of non-small cell lung cancer (NSCLC), and discuss biomarkers associated with the treatment responses, mechanisms underlying resistance and strategies to overcome resistance. The success of immune checkpoint blockade therapies is driven by immunogenicity of tumor cells, which is associated with mutation burden and neoantigen burden in cancers. Lymphocyte infiltration in cancer tissues and interferon-γ-induced PD-L1 expression in tumor microenvironments may serve as surrogate biomarkers for adaptive immune resistance and likelihood of responses to immune checkpoint blockade therapy. In contrast, weak immunogenicity of, and/or impaired antigen presentation in, tumor cells are primary causes of resistance to these therapies. Thus, approaches that increase immunogenicity of cancer cells and/or enhance immune cell recruitment to cancer sites will likely overcome resistance to immunotherapy.
近年来，靶向治疗和免疫疗法的突破彻底改变了肺癌的治疗方式，肺癌是美国和全球癌症相关死亡的主要原因。在这里，我们概述了免疫检查点阻断疗法在治疗非小细胞肺癌（NSCLC）方面的最新进展，并讨论了与治疗反应相关的生物标志物、耐药机制以及克服耐药的策略。免疫检查点阻断疗法的成功得益于肿瘤细胞的免疫原性，这与癌症中的突变负担和新抗原负担有关。肿瘤组织中的淋巴细胞浸润和肿瘤微环境中干扰素-γ诱导的 PD-L1 表达可以作为适应性免疫抵抗和对免疫检查点阻断治疗反应可能性的替代生物标志物。相比之下，肿瘤细胞的免疫原性较弱和/或抗原呈递受损是对这些治疗产生耐药的主要原因。因此，增加癌细胞的免疫原性和/或增强免疫细胞向肿瘤部位的募集的方法可能会克服免疫治疗的耐药性。
