Narrative review: immunotherapy in anaplastic lymphoma kinase (ALK)+ lung cancer-current status and future directions.

Content Provider	Europe PMC
Author	Schenk, Erin L.
Copyright Year	2023
Abstract	Background and ObjectivePatients 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.MethodsTo 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 FindingsIn 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.ConclusionsImmune 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.
ISSN	22186751
Journal	Translational Lung Cancer Research
Volume Number	12
PubMed Central reference number	PMC9989807
Issue Number	2
PubMed reference number	36895933
e-ISSN	22264477
DOI	10.21037/tlcr-22-883
Language	English
Publisher	AME Publishing Company
Publisher Date	2023-02-25
Access Restriction	Open
Rights License	Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0. 2023 Translational Lung Cancer Research. All rights reserved.
Subject Keyword	Anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) tumor microenvironment (TME) immunotherapy
Content Type	Text
Resource Type	Article
Subject	Oncology