免疫疗法
肺癌
肿瘤微环境
后天抵抗
癌症研究
联合疗法
生物
非小细胞肺癌
靶向治疗
肿瘤科
癌基因
癌症
生物信息学
医学
内科学
A549电池
细胞周期
肿瘤细胞
作者
Lena Horvath,Bernard Thienpont,Liyun Zhao,Dominik Wolf,Andreas Pircher
标识
DOI:10.1186/s12943-020-01260-z
摘要
Abstract Immunotherapy (IO) has revolutionized the therapy landscape of non-small cell lung cancer (NSCLC), significantly prolonging the overall survival (OS) of advanced stage patients. Over the recent years IO therapy has been broadly integrated into the first-line setting of non-oncogene driven NSCLC, either in combination with chemotherapy, or in selected patients with PD-L1 high expression as monotherapy. Still, a significant proportion of patients suffer from disease progression. A better understanding of resistance mechanisms depicts a central goal to avoid or overcome IO resistance and to improve patient outcome. We here review major cellular and molecular pathways within the tumor microenvironment (TME) that may impact the evolution of IO resistance. We summarize upcoming treatment options after IO resistance including novel IO targets (e.g. RIG-I, STING) as well as interesting combinational approaches such as IO combined with anti-angiogenic agents or metabolic targets (e.g. IDO-1, adenosine signaling, arginase). By discussing the fundamental mode of action of IO within the TME, we aim to understand and manage IO resistance and to seed new ideas for effective therapeutic IO concepts.
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