BREAKTHROUGH IMMUNOMODULATION THERAPY IN IDIOPATHIC PULMONARY FIBROSIS: A NARRATIVE LITERATURE REVIEW
Main Article Content
Amiruddin
Faridj Maulana Amir
Background: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis. Several antifibrotics such as pirfenidone and nintedanib have been shown to slow the decline in lung function but cannot stop the ongoing or existing fibrosis process. Recent evidence suggests that immune dysregulation, including macrophage activation and PD-L1 expression on fibroblasts, plays a key role in the pathogenesis of IPF, thus encouraging the emergence of potential immunomodulation therapies. Methods: This paper attempts to review several English-language literature from 2015–2025 through PubMed, Scopus, and ClinicalTrials.gov. Articles relevant to immunotherapy, immunomodulators, or immune mechanisms in IPF were included, while non-scientific or non-immune-related publications were ignored. Results: A total of 15 primary publications were identified. Immunotherapy approaches such as PD-L1 inhibition, Treg activation, and IL-4/IL-13 blockade have shown antifibrotic and immunoregulatory effects. New agents such as the TNIK inhibitor (ISM001-055), the peptide LTI-03, and CAR-Treg therapy have shown promising early results in translational models and early-phase clinical trials. Conclusion: Immunotherapy has the potential to be a novel approach to IPF management by targeting the immune microenvironment. Further trials are needed to ensure safety and efficacy for long-term treatment.
Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of idiopathic pulmonary fibrosis: an official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198(5):e44–68.
https://doi.org/10.1164/rccm.201807-1255ST
George PM, Wells AU, Jenkins RG. Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy. Lancet Respir Med. 2020;8(8):807–15.
https://doi.org/10.1016/S2213-2600(20)30225-3
Hirani N, Mackinnon AC, Nicol L, et al. Target inhibition of galectin-3 by inhaled TD139 in patients with idiopathic pulmonary fibrosis. Eur Respir J. 2021;57(3):2002559.
https://doi.org/10.1183/13993003.02559-2020
Ziegenhagen MW, Zissel G, Schlaak M, Müller-Quernheim J. Fibrosing alveolitis: immunopathogenesis and immunotherapy. Eur Respir J. 2019;53(2):1801903.
https://doi.org/10.1183/13993003.01903-2018
Saito T, Kuronuma K, Monma T, et al. PD-L1 expression on alveolar macrophages and lung epithelial cells in idiopathic pulmonary fibrosis. Sci Rep. 2018;8:17347.
https://doi.org/10.1038/s41598-018-35608-8
Nakashima T, Yokoyama A, Inoue Y, et al. PD-1/PD-L1 blockade ameliorates fibrosis in a murine model of IPF. Am J Respir Cell Mol Biol. 2020;63(4):546–56.
https://doi.org/10.1165/rcmb.2019-0273OC
Tashiro J, Rubio GA, Limper AH, Williams K, et al. Exploring animal models that resemble idiopathic pulmonary fibrosis. Front Med (Lausanne). 2017;4:118.
https://doi.org/10.3389/fmed.2017.00118
Wynn TA, Ramalingam TR. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med. 2019;25(7):1028–40.
https://doi.org/10.1038/s41591-019-0469-0
Tang J, Li Z, Lu L, et al. CAR-T regulatory cells suppress lung fibrosis via TGF-β pathway modulation in preclinical model. Nat Commun. 2022;13:5412.
https://doi.org/10.1038/s41467-022-33174-2
Moore BB, Fry C, Zhou Y, Murray S, et al. Reprogramming macrophage polarization as a novel immunotherapy strategy in pulmonary fibrosis. Am J Respir Crit Care Med. 2021;204(4):438–49.
https://doi.org/10.1164/rccm.202012-4348OC
Richeldi L, Varone F, Bergna M, et al. Pharmacological management of idiopathic pulmonary fibrosis: current and emerging options. Drugs. 2020;80(12):1257–72.
https://doi.org/10.1007/s40265-020-01349-4
Raghu G, van den Blink B, Hamblin MJ, et al. Effect of ISM001-055, a novel TNIK inhibitor, in idiopathic pulmonary fibrosis: phase 1 trial results. Am J Respir Crit Care Med. 2022;205(9):A2868.
https://doi.org/10.1164/rccm.202205-2868OC
Martinez FJ, Safrin S, Weycker D, et al. The clinical course of idiopathic pulmonary fibrosis. Ann Intern Med. 2017;167(8):556–63.
https://doi.org/10.7326/M17-1203
Noble PW, Albera C, Bradford WZ, et al. Pirfenidone and nintedanib: real-world data and future direction of antifibrotic therapy. Eur Respir Rev. 2019;28(153):190082.
https://doi.org/10.1183/16000617.0082-2019
Cottin V, Hirani NA, Hotchkin DL, et al. Updated international guidelines for idiopathic interstitial pneumonias. Eur Respir J. 2022;59(3):2103191.
