Neoadjuvant immunotherapy for non-small cell lung cancer:Opportunities and challenges  

作　　者：Junjie Hu Jing Zhang Shiyue Wan Peng Zhang 

机构地区：[1]School of Medicine,Tongji University,Shanghai 200092,China [2]Department of Thoracic Surgery,Shanghai Pulmonary Hospital,School of Medicine,Tongji University,Shanghai 200433,China [3]Central Laboratory,Shanghai Pulmonary Hospital,School of Medicine,Tongji University,Shanghai 200433,China [4]The 1st School of Medicine,the 1st Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang 325000,China [5]Department of Thoracic Surgery,The First Affiliated Hospital of Shihezi University Medical College,Shihezi,Xinjiang 832000,China

出　　处：《Chinese Medical Journal Pulmonary and Critical Care Medicine》2024年第4期224-239,共16页呼吸与危重症医学(英文)

基　　金：supported by the National Natural Science Foundation of China(Nos.82125001 and 82473368);the Innovation Program of Shanghai Municipal Education Commission(No.2023ZKZD33);Shanghai Pulmonary Hospital(Nos.FKCX2304 and FKLY20004).

摘　　要：Immune checkpoint inhibitors(ICIs)have transformed the treatment landscape for resectable non-small cell lung cancer.Numerous trials have explored the use of ICIs,either as monotherapy or in combination with other therapies,in the neoadjuvant setting for stage Ⅰ-Ⅲ non-small cell lung cancer.Most trials have demonstrated neoadjuvant immunotherapy to be safe and to have remarkable efficacy,with a high pathological response rate and significantly improved event-free survival.This review summarizes the findings of Phase Ⅰ-Ⅲ clinical trials investigating various neoadjuvant regimens,including ICI monotherapy,ICI therapy combined with chemother-apy,ICI plus anti-angiogenic therapy,dual ICI therapy,and ICI therapy in combination with radiotherapy or chemoradiotherapy.We discuss the benefits and outcomes associated with each approach.Despite the results being promising,several unresolved issues remain,including identification of reliable biomarkers,the appropri-ate duration of therapy,the optimal treatment regimen for tumors with high programmed cell death ligand 1(PD-L1)expression,the false-negative pathological complete response rate,and the role of digital pathology in assessing the response to treatment.Resistance to immunotherapy,in particular,remains a significant barrier to effective use of ICIs.Given the critical influence of the tumor microenvironment(TME)on the response to treat-ment,we examine the characteristics of the TME in both responsive and resistant tumors as well as the dynamic changes that occur in the TME in response to neoadjuvant immunotherapy.We also summarize the mechanisms underlying T cell responses following neoadjuvant immunotherapy and provide a perspective on strategies to enhance the understanding of tumor heterogeneity,therapy-driven TME remodeling,and overcoming resistance to therapy.Finally,we propose future directions for advancements in personalized neoadjuvant immunotherapy.

关 键 词：Lung cancer Neoadjuvant immunotherapy Combinatorial therapy BIOMARKER Tumor microenvironment 

分 类 号：R73[医药卫生—肿瘤]