Immunotherapy for non-small cell lung cancers: biomarkers for predicting responses and strategies to overcome resistance.
Immunotherapy for non-small cell lung cancers: biomarkers for predicting responses and strategies to overcome resistance.
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DOI：
10.1186/s12885-018-4990-5
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发表时间：
2018-11-08
期刊：
影响因子：
3.8
通讯作者：
Fang B
中科院分区：
文献类型：
--
作者：
Pu X;Wu L;Su D;Mao W;Fang B
最近在靶向治疗和免疫治疗方面的突破使肺癌的治疗发生了革命性的变化，肺癌是美国和世界范围内与癌症相关的死亡的主要原因。本文综述了免疫检查点阻断治疗非小细胞肺癌(NSCLC)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。免疫检查点阻断治疗的成功是由肿瘤细胞的免疫原性推动的，而肿瘤细胞的免疫原性与肿瘤中的突变负荷和新抗原负荷有关。肿瘤组织中的淋巴细胞浸润和干扰素-γ诱导的肿瘤微环境中PD-L1的表达可能作为获得性免疫抵抗和免疫检查点阻断治疗应答的替代生物标志物。相反，肿瘤细胞免疫原性弱和/或抗原提呈受损是抵抗这些治疗的主要原因。因此，提高癌细胞的免疫原性和/或增强免疫细胞向癌症部位募集的方法可能会克服免疫治疗的阻力。
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.
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影响因子：
64.5
作者：
Benci JL;Xu B;Qiu Y;Wu TJ;Dada H;Twyman-Saint Victor C;Cucolo L;Lee DSM;Pauken KE;Huang AC;Gangadhar TC;Amaravadi RK;Schuchter LM;Feldman MD;Ishwaran H;Vonderheide RH;Maity A;Wherry EJ;Minn AJ
通讯作者：
Minn AJ
影响因子：
56.9
作者：
Butcher, EC;Picker, LJ
通讯作者：
Picker, LJ
影响因子：
15.9
作者：
Cohen, Cyrille J.;Gartner, Jared J.;Robbins, Paul F.
通讯作者：
Robbins, Paul F.
影响因子：
4.4
作者：
Djenidi, Faycal;Adam, Julien;Mami-Chouaib, Fathia
通讯作者：
Mami-Chouaib, Fathia
影响因子：
30.5
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
通讯作者：
Wherry, E. John