AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025350362
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REVIEW ARTICLE

An update on the role of immune checkpoint inhibitors in lung cancer: A narrative systematic review

Inês Sousa1† ,  Diana Martins1,2,3,4† ,  Fernando Mendes1,2,3,4,5†*
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1 Polytechnic University of Coimbra, Coimbra Health School (ESTeSC), Coimbra, Portugal
2 H&TRC—Health and Technology Research Center, Coimbra Health School, Polytechnic University of Coimbra, Coimbra, Portugal
3 Biophysics Institute of Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR)Area of Environment Genetics and Oncobiology (CIMAGO), University of Coimbra, Coimbra, Portugal
4 Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
5 European Association for Professions in Biomedical Sciences, Brussels, Belgium
†These authors contributed equally to this work.
EJMO, 025350362 https://doi.org/10.36922/EJMO025350362
Received: 27 August 2025 | Revised: 5 November 2025 | Accepted: 19 November 2025 | Published online: 18 December 2025
(This article belongs to the Special Issue Tumor Immune Microenvironment and Intervention Strategies)
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, and its aggressive nature necessitates the development of alternative therapeutic strategies. Immune checkpoint inhibitors (ICIs) have shown remarkable success in LC treatment. Despite advances with programmed cell death protein-1/programmed cell death ligand-1 inhibitors, many patients experience limited or short-lived responses, prompting interest in novel ICIs such as T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domain (TIGIT), lymphocyte-activation gene 3 (LAG-3), and indoleamine 2,3-dioxygenase 1 (IDO-1).

Objectives: This narrative systematic review aimed to assess the clinical efficacy and safety of these novel ICIs compared to standard ICI therapy in LC.

Methods: A systematic literature search was conducted across PubMed, Web of Science, and ClinicalTrials.gov. The search covered studies published from January 2020 to January 2025, to identify randomized controlled trials (RCTs) evaluating novel ICIs in LC. Due to substantial heterogeneity in study design, intervention targets, and outcome reporting, findings were synthesized narratively in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using RoB 2.

Results: Five RCTs involving a total of 825 patients were included. TIGIT inhibition demonstrated benefit in progression-free survival and response rate. LAG-3 inhibitors showed mixed efficacy, with potential dose-related differences. IDO-1 inhibitors failed to improve outcomes compared with standard ICI. Reporting quality varied, with concerns regarding incomplete outcome data in some trials.

Conclusion: These findings suggest promise for novel ICIs but are limited by small study numbers, methodological bias, and clinical heterogeneity. Larger, well-designed Phase III trials are required to validate these results.

Keywords
Lung cancer
Immune checkpoint inhibitors
Immunotherapy
Narrative systematic review
Funding
This research was funded by the Foundation for Science and Technology/Ministry of Science, Technology, and Higher Education (project numbers UIDP/05608/2020 and UIDB/05608/2020).
Conflict of interest
The authors declare that they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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