肿瘤细胞治疗研究
英文原题：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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源自当前及不断演进的 ALK+ 非小细胞肺癌肿瘤微环境认知的免疫调节策略，可能在 PD-1/PD-L1 免疫治疗之外对 ALK+ 非小细胞肺癌发挥作用。
转移性间变性淋巴瘤激酶阳性（ALK⁺）非小细胞肺癌（NSCLC）患者常可通过靶向治疗控制疾病多年，但最终会产生耐药并进展。多项临床试图将PD-1/PD-L1免疫疗法纳入ALK⁺ NSCLC治疗方案，但导致明显毒性，未能明确改善患者结局。临床试验、转化研究和临床前模型观察提示，免疫系统与ALK⁺ NSCLC相互作用，且靶向治疗开始后这一相互作用增强。本综述旨在总结ALK⁺ NSCLC患者当前和潜在免疫治疗方法的现有知识。
为确定相关文献和临床试验，我们检索PubMed.gov和ClinicalTrials.gov数据库，关键词为“ALK”和“lung cancer”。此外，PubMed检索进一步加入“immunotherapy”“tumor microenvironment or TME”“PD-1”和“T cells”等词。临床试验检索限于干预性研究。主要内容与发现：本综述更新ALK⁺ NSCLC的PD-1/PD-L1免疫治疗现状，并结合ALK⁺ NSCLC肿瘤微环境（TME）患者级及转化研究数据，重点介绍替代免疫治疗策略。多项研究观察到，靶向治疗开始后ALK⁺ NSCLC TME中的CD8⁺ T细胞增加。综述还介绍了增强这一过程的疗法，包括TIL（肿瘤浸润淋巴细胞）疗法、改造细胞因子和溶瘤病毒。此外，还讨论了先天免疫细胞在酪氨酸激酶抑制剂（TKI）介导肿瘤细胞清除中的作用，该作用可能成为通过促进癌细胞吞噬开发新型免疫疗法的未来靶点。
基于当前及不断发展的ALK⁺ NSCLC TME知识，免疫调节策略可能在PD-1/PD-L1免疫疗法之外，对ALK⁺ NSCLC治疗发挥作用。
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. KEY CONTENT AND FINDINGS: 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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