Immune Checkpoints as Promising Targets for the Treatment of Idiopathic Pulmonary Fibrosis?

Abstract

Idiopathic pulmonary fibrosis is a rare, progressive and fatal lung disease which affects approximately 5 million persons worldwide. Although pirfenidone and/or nintedanib treatment improves patients’ wellbeing, the prognosis of IPF remains poor with 5-year mortality rates still ranging from 70 to 80%. The promise of the anti-cancer agent nintedanib in IPF, in combination with the recent notion that IPF shares several pathogenic pathways with cancer, raised hope that immune checkpoint inhibitors, the novel revolutionary anticancer agents, could also be the eagerly awaited ground-breaking and unconventional novel treatment modality limiting IPF-related morbidity/mortality. In the current review, we analyse the available literature on immune checkpoint proteins in IPF to explore whether immune checkpoint inhibition may be as promising in IPF as it is in cancer. We conclude that despite several promising papers showing that inhibiting specific immune checkpoint proteins limits pulmonary fibrosis, overall the data seem to argue against a general role of immune checkpoint inhibition in IPF and suggest that only PD-1/PD-L1 inhibition may be beneficial.

Safety and effectiveness of pirfenidone combined with carboplatin‐based chemotherapy in patients with idiopathic pulmonary fibrosis and non‐small cell lung cancer: A retrospective cohort study

“…37 By blocking PD-1, ICIs invigorate T lymphocytes and enable CD8 + T lymphocytes to engage in the cytotoxic killing of cancer cells. 37 Meanwhile, fibroblasts and CD4 + T lymphocytes in IPF have been shown to express PD-L1 and PD-1, respectively; 38,39 the upregulation of both is associated with pulmonary fibrosis. 38,39 Hence, PD-1/PD-L1 checkpoint might be associated with fibroblast immune editing and subsequent invasion and metastases to other organs in IPF.…”

“…Pirfenidone combined with ICIs, particularly anti‐PD‐1 antibodies, might be safe for patients with IPF and NSCLC. ICIs have been developed to target immune checkpoints commonly used by cancer cells in immune editing and block cancer cell evasion from immune detection 37 . By blocking PD‐1, ICIs invigorate T lymphocytes and enable CD8 + T lymphocytes to engage in the cytotoxic killing of cancer cells 37 .…”

Post-intubation subglottic stenosis: aetiology at the cellular and molecular level

“…Thus, PD-1/ PD-L1 inhibitors may have potential for the treatment of fibrosis-related diseases. Current evidence indicates that the potential of PD-1/PD-L1 inhibitors does not expand to all checkpoint inhibitors [140], and that at least part of the function of the PD-1/PD-L1 axis in fibroblasts is independent of its well characterised immune-regulatory function [138].…”

U three protein 14a (UTP14A) promotes tumour proliferation and metastasis via the PERK/eIF2a/GRP78 signalling pathway in oesophageal squamous cell carcinoma

“…Therefore, comprehensive treatment with chemoradiation has become an indispensable treatment method. Although treatment has improved in recent years, the prognosis of patients with oesophageal cancer is still not optimistic, and the 5-year survival rate is only 15.0% to 20.9% 1 . Early invasion and metastasis of tumour cells are the main reasons for poor prognosis in patients with ESCC (oesophageal squamous cell carcinoma); therefore, it is necessary to explore the possible mechanisms of oesophageal cancer invasion and metastasis 2 , 3 .…”