Spella Magda, Stathopoulos Georgios T
Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, 26504 Achaia, Greece.
Comprehensive Pneumology Center (CPC), Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich-German Research Center for Environmental Health, Member of the German Center for Lung Research, 81377 Munich, Germany.
Cancers (Basel). 2021 Jan 21;13(3):384. doi: 10.3390/cancers13030384.
Lung cancer is the leading cancer killer worldwide, imposing grievous challenges for patients and clinicians. The incidence of lung adenocarcinoma (LUAD), the main histologic subtype of lung cancer, is still increasing in current-, ex-, and even non-smokers, whereas its five-year survival rate is approximately 15% as the vast majority of patients usually present with advanced disease at the time of diagnosis. The generation of novel drugs targeting key disease driver mutations has created optimism for the treatment of LUAD, but, as these mutations are not universal, this therapeutic line benefits only a subset of patients. More recently, the advent of targeted immunotherapies and their documented clinical efficacy in many different cancers, including LUAD, have started to change cancer management. Immunotherapies have been developed in order to overcome the cancer's ability to develop mechanisms of immune resistance, i.e., to adapt to and evade the host inflammatory and immune responses. Identifying a cancer's immune resistance mechanisms will likely advance the development of personalized immunotherapies. This review examines the key pathways of immune resistance at play in LUAD and explores therapeutic strategies which can unleash potent antitumor immune responses and significantly improve therapeutic efficacy, quality of life, and survival in LUAD.
肺癌是全球主要的癌症杀手，给患者和临床医生带来了严峻挑战。肺腺癌（LUAD）作为肺癌的主要组织学亚型，在当前吸烟者、既往吸烟者甚至从不吸烟者中的发病率仍在上升，而其五年生存率约为15%，因为绝大多数患者在诊断时通常已处于晚期。针对关键疾病驱动基因突变的新型药物的出现为LUAD的治疗带来了希望，但由于这些突变并不普遍，这种治疗方法仅使一部分患者受益。最近，靶向免疫疗法的出现及其在包括LUAD在内的许多不同癌症中的临床疗效记录已经开始改变癌症治疗模式。开发免疫疗法是为了克服癌症产生免疫抵抗机制的能力，即适应并逃避宿主的炎症和免疫反应。识别癌症的免疫抵抗机制可能会推动个性化免疫疗法的发展。本综述探讨了LUAD中发挥作用的关键免疫抵抗途径，并探索了能够释放强大抗肿瘤免疫反应并显著提高LUAD治疗效果、生活质量和生存率的治疗策略。
