Narrative review: immunotherapy in anaplastic lymphoma kinase (ALK)+ lung cancer-current status and future directions.
Narrative review: immunotherapy in anaplastic lymphoma kinase (ALK)+ lung cancer-current status and future directions.
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DOI：
10.21037/tlcr-22-883
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发表时间：
2023-02-28
影响因子：
4
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转移性间变性淋巴瘤激酶（ALK）+非小细胞肺癌（NSCLC）患者通常在靶向治疗后经历多年的疾病控制，但疾病最终产生耐药性并进展。将PD-1/PD-L1免疫疗法纳入ALK+ NSCLC治疗模式的多项临床试验已导致显著毒性，但患者结局未得到明显改善。临床试验、转化研究和临床前模型的观察结果表明，免疫系统与ALK+ NSCLC相互作用，并且这种相互作用随着靶向治疗的开始而增强。本综述的目的是总结迄今为止关于ALK+ NSCLC患者当前和潜在免疫治疗方法的知识。为了识别相关文献和临床试验，使用关键词“ALK”和“肺癌”查询数据库PubMed.gov和ClinicalTrials.gov。PubMed检索进一步细化了“免疫疗法”、“肿瘤微环境或TME”、“PD-1”和“T细胞”等术语。临床试验检索仅限于干预性研究。在本综述中，更新了PD-1/PD-L1免疫治疗ALK+ NSCLC的现状，并在现有患者水平和ALK+ NSCLC肿瘤微环境（TME）转化数据的背景下强调了替代免疫治疗方法。在多项研究中，在靶向治疗开始时观察到ALK+ NSCLC TME内的CD 8 + T细胞增加。治疗，以增加这包括肿瘤浸润淋巴细胞（TIL）治疗，修饰的细胞因子，溶瘤病毒进行审查。此外，先天免疫细胞在TKI介导的肿瘤细胞清除中的贡献被讨论为促进癌细胞吞噬的新型免疫治疗方法的未来目标。基于当前和不断发展的ALK+ NSCLC TME知识的免疫调节策略在ALK+ NSCLC中的作用可能超出基于PD-1/PD-L1的免疫治疗。
Patients with metastatic anaplastic lymphoma kinase (ALK)+ non-small cell lung cancer (NSCLC) often experience years of disease control on targeted therapies but the disease eventually develops resistance and progresses. Multiple clinical trial efforts to incorporate PD-1/PD-L1 immunotherapy into the treatment paradigm for ALK+ NSCLC have resulted in significant toxicities without clear improvement in patient outcomes. Observations from clinical trials, translational studies, and preclinical models suggest the immune system interacts with ALK+ NSCLC and this interaction is heightened with the initiation of targeted therapy. The objective of this review is to summarize knowledge to date about current and potential immunotherapy approaches for patients with ALK+ NSCLC. To identify the relevant literature and clinical trials the databases PubMed.gov and ClinicalTrials.gov were queried with keywords “ALK” and “lung cancer”. PubMed search was further refined with terms such as “immunotherapy”, “tumor microenvironment or TME”, “PD-1”, and “T cells”. The search for clinical trials was limited to interventional studies. In this review, the current status of PD-1/PD-L1 immunotherapy for ALK+ NSCLC is updated and alternative immunotherapy approaches are highlighted in the context of available patient level and translational data on the ALK+ NSCLC tumor microenvironment (TME). An increase in CD8+ T cells within the ALK+ NSCLC TME has been observed with targeted therapy initiation across multiple studies. Therapies to augment this including tumor infiltrating lymphocyte (TIL) therapy, modified cytokines, and oncolytic viruses are reviewed. Furthermore, the contribution of innate immune cells in TKI mediated tumor cell clearance is discussed as a future target for novel immunotherapy approaches that promote cancer cell phagocytosis. Immune modulating strategies derived from current and evolving knowledge of the ALK+ NSCLC TME may have a role in ALK+ NSCLC beyond PD-1/PD-L1 based immunotherapy.
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影响因子：
--
作者：
Awad MM;Mastini C;Blasco RB;Mologni L;Voena C;Mussolin L;Mach SL;Adeni AE;Lydon CA;Sholl LM;Jänne PA;Chiarle R
通讯作者：
Chiarle R
影响因子：
82.9
作者：
Creelan BC;Wang C;Teer JK;Toloza EM;Yao J;Kim S;Landin AM;Mullinax JE;Saller JJ;Saltos AN;Noyes DR;Montoya LB;Curry W;Pilon-Thomas SA;Chiappori AA;Tanvetyanon T;Kaye FJ;Thompson ZJ;Yoder SJ;Fang B;Koomen JM;Sarnaik AA;Chen DT;Conejo-Garcia JR;Haura EB;Antonia SJ
通讯作者：
Antonia SJ
影响因子：
7.2
作者：
Fang Y;Wang Y;Zeng D;Zhi S;Shu T;Huang N;Zheng S;Wu J;Liu Y;Huang G;Xue Y;Bin J;Liao Y;Shi M;Liao W
通讯作者：
Liao W
影响因子：
6.4
作者：
Ait-Taharl, K;Cerundolo, V;Pulford, K
通讯作者：
Pulford, K
影响因子：
20.4
作者：
Cho, Byoung Chul;Obermannova, Radka;Dziadziuszko, Rafal
通讯作者：
Dziadziuszko, Rafal