Observational studyThe Journal of clinical investigation2019
The alveolar immune cell landscape is dysregulated in checkpoint inhibitor pneumonitis.
Observational study in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 8 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
128 citing papers in PubMed, 8 syntheses or guidelines pooled it, 190 citations in OpenAlex.
- Bronchoalveolar lavage fluid lymphocytosis in immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer: a systematic review and meta-analysis.BMC pulmonary medicine · 2026Pooled it
- Efficacy and safety of immunotherapy in anaplastic thyroid carcinoma: a systematic review and meta-analysis.International journal of surgery (London, England) · 2026Pooled it
- Monocyte-related markers as predictors of immune checkpoint inhibitor efficacy and immune-related adverse events: a systematic review and meta-analysis.Cancer metastasis reviews · 2025Pooled it
- Risk and safety profile in checkpoint inhibitors on non-small-cel lung cancer: A systematic review.Human vaccines & immunotherapeutics · 2024Pooled it
- Corticosteroid-resistant immune-related adverse events: a systematic review.Journal for immunotherapy of cancer · 2024Pooled it
- Pooled it
- Pooled it
- Immune-Related Pneumonitis Was Decreased by Addition of Chemotherapy with PD-1/L1 Inhibitors: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials (RCTs).Current oncology (Toronto, Ont.) · 2022Pooled it
- A nomogram model for predicting the risk of checkpoint inhibitor-related pneumonitis for patients with advanced non-small-cell lung cancer.Cancer medicine · 2023Trial
- Dexamethasone-Induced FKBP51 Expression in CD4Frontiers in immunology · 2021Trial
- Inhibitory receptor profiles for joint prediction of benefit and toxicity in immune checkpoint blockade.iScience · 2026Review
- Pneumonitis Associated with Immune Checkpoint Inhibitors and Targeted Anticancer Therapies: A Retrospective Case Series of 12 Patients.Diseases (Basel, Switzerland) · 2026Article
- Immune Checkpoint Inhibitor-Related Pneumonitis in Renal Cell Carcinoma: Clinical Features, Mechanisms, and Lessons from Lung Cancer.Biomolecules · 2026Review
- Single-cell hdWGCNA identifies checkpoint inhibitor pneumonitis-linked CD4 + T-cell subsets driving immunotherapy response and prognosis in lung cancer.Journal of cancer research and clinical oncology · 2026Article
- Preliminary exploration of the role of CD8Biomedical reports · 2026Article
- Case reports of immune-associated pneumonia with radiological cavity formation.BMC pulmonary medicine · 2026Article
- Pulmonary toxicity of immune checkpoint inhibitors.Breathe (Sheffield, England) · 2026Review
- Radiation Dose-Dependent and -Independent Pulmonary Infiltrates in Patients with High-Grade Pneumonitis After Radiochemotherapy and Durvalumab Consolidation for Stage III NSCLC.Diagnostics (Basel, Switzerland) · 2026Article
- When Checkpoint Inhibitors Break Barriers: Mechanisms and Challenges of irAEs of the Skin, Gastrointestinal Tract, and Lung.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Targeting NLRP3 inflammasome: a novel strategy for improving immune checkpoint inhibitor-associated pneumonitis.Translational lung cancer research · 2026Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCheckpoint inhibitor pneumonitis (CIP) is a highly morbid complication of immune checkpoint immunotherapy (ICI), one which precludes the continuation of ICI. Yet, the mechanistic underpinnings of CIP are unknown.
methodsTo better understand the mechanism of lung injury in CIP, we prospectively collected bronchoalveolar lavage (BAL) samples in ICI-treated patients with (n=12) and without CIP (n=6), prior to initiation of first-line therapy for CIP (high dose corticosteroids. We analyzed BAL immune cell populations using a combination of traditional multicolor flow cytometry gating, unsupervised clustering analysis and BAL supernatant cytokine measurements.
resultsWe found increased BAL lymphocytosis, predominantly CD4+ T cells, in CIP. Specifically, we observed increased numbers of BAL central memory T-cells (Tcm), evidence of Type I polarization, and decreased expression of CTLA-4 and PD-1 in BAL Tregs, suggesting both activation of pro-inflammatory subsets and an attenuated suppressive phenotype. CIP BAL myeloid immune populations displayed enhanced expression of IL-1β and decreased expression of counter-regulatory IL-1RA. We observed increased levels of T cell chemoattractants in the BAL supernatant, consistent with our pro-inflammatory, lymphocytic cellular landscape.
conclusionWe observe several immune cell subpopulations that are dysregulated in CIP, which may represent possible targets that could lead to therapeutics for this morbid immune related adverse event.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.