# Bronchoalveolar lavage fluid in immune checkpoint inhibitor-related pneumonitis: from pathophysiological window to a precision diagnostic tool

**Authors:** Zheng Linpeng, Yang Jing, Qi Yaxian, Lin Fenglin, Chen Xiewan, Sun Jianguo

PMC · DOI: 10.3389/fimmu.2026.1788186 · Frontiers in Immunology · 2026-02-18

## TL;DR

This paper explores how bronchoalveolar lavage fluid can help diagnose and understand immune checkpoint inhibitor-related pneumonitis by analyzing immune responses and potential biomarkers.

## Contribution

The paper highlights BALF as a precision diagnostic tool and identifies biomarkers like CCL18, IL-6, and IP-10 for early detection and monitoring of pneumonitis.

## Key findings

- BALF lymphocytosis is a key diagnostic sign for immune checkpoint inhibitor-related pneumonitis.
- Abnormal T-cell activation and myeloid cell reprogramming are central to the disease's development.
- Biomarkers like CCL18, IL-6, and IP-10 may aid in early detection and disease monitoring.

## Abstract

Immune checkpoint inhibitor related pneumonitis is a serious adverse reaction with diverse clinical and radiologic patterns, which make both diagnosis and treatment challenging. Therefore, understanding its underlying biology is crucial for improving clinical management. Bronchoalveolar lavage fluid provides a minimally invasive way to explore the lung immune environment, and it supports cytologic, molecular, and multi-omics analyses. In particular, BALF lymphocytosis serves as a key diagnostic sign. Furthermore, single-cell sequencing has revealed that abnormal T-cell activation and myeloid cell reprogramming play central roles in the development of CIP. These findings have, in turn, led to the identification of potential biomarkers such as CCL18, IL-6, and IP-10 for early detection and disease monitoring. However, the absence of standardized sampling and interpretation methods still limits the reproducibility of results and the broader application of BALF analysis in clinical practice. In the future, integrating BALF-derived data into artificial intelligence frameworks may enhance diagnostic precision and guide personalized therapy. Overall, BALF represents a valuable platform for refining CIP classification, clarifying disease mechanisms, and supporting the development of targeted treatments.

## Linked entities

- **Proteins:** CCL18 (C-C motif chemokine ligand 18), IL6 (interleukin 6), CXCL10 (C-X-C motif chemokine ligand 10)
- **Diseases:** pneumonitis (MONDO:0043905)

## Full-text entities

- **Genes:** IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CXCR3 (C-X-C motif chemokine receptor 3) [NCBI Gene 2833] {aka CD182, CD183, CKR-L2, CMKAR3, GPR9, IP10-R}, CXCL11 (C-X-C motif chemokine ligand 11) [NCBI Gene 6373] {aka H174, I-TAC, IP-9, IP9, SCYB11, SCYB9B}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CXCL13 (C-X-C motif chemokine ligand 13) [NCBI Gene 10563] {aka ANGIE, ANGIE2, BCA-1, BCA1, BLC, BLR1L}, CCL18 (C-C motif chemokine ligand 18) [NCBI Gene 6362] {aka AMAC-1, AMAC1, CKb7, DC-CK1, DCCK1, MIP-4}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, FASLG (Fas ligand) [NCBI Gene 356] {aka ALPS1B, APT1LG1, APTL, CD178, CD95-L, CD95L}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, S100A9 (S100 calcium binding protein A9) [NCBI Gene 6280] {aka 60B8AG, CAGB, CFAG, CGLB, L1AG, LIAG}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, CXCR6 (C-X-C motif chemokine receptor 6) [NCBI Gene 10663] {aka BONZO, CD186, CDw186, STRL33, TYMSTR}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CXCL9 (C-X-C motif chemokine ligand 9) [NCBI Gene 4283] {aka CMK, Humig, MIG, SCYB9, crg-10}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, LAMP3 (lysosome associated membrane protein 3) [NCBI Gene 27074] {aka CD208, DC LAMP, DC-LAMP, DCLAMP, LAMP, LAMP-3}
- **Diseases:** cough (MESH:D003371), acute lung injury (MESH:D055371), AEP (MESH:D015472), asthma (MESH:D001249), eosinophilia (MESH:D004802), lung injury (MESH:D055370), legionella (MESH:D007877), infection (MESH:D007239), dyspnea (MESH:D004417), lung cancer (MESH:D008175), IPF (MESH:D054990), Radiation Pneumonitis (MESH:D017564), sarcoidosis (MESH:D012507), lung diseases (MESH:D008171), CIP (MESH:C565467), deterioration of respiratory function (MESH:D012120), Tumor (MESH:D009369), influenza virus (MESH:D007251), death (MESH:D003643), connective tissue disease (MESH:D003240), Neutrophilia (MESH:C563010), pulmonary infection (MESH:D012141), inflammation (MESH:D007249), PCP (MESH:D011020), metastases (MESH:D009362), critically ill (MESH:D016638), NSCLC (MESH:D002289), hypoxemia (MESH:D000860), infectious diseases (MESH:D003141), airway obstruction (MESH:D000402), aspergillus (MESH:D001228), hematologic malignancies (MESH:D019337), ARDS (MESH:D012128), BALF lymphocytosis (MESH:D008218), COPD (MESH:D029424), Candida albicans infection (MESH:D002177), ILD (MESH:D017563), bacterial pneumonia (MESH:D018410), Pneumonitis (MESH:D011014), immune-mediated diseases (MESH:C567355), allergic disease (MESH:D004342), hemoptysis (MESH:D006469), respiratory failure (MESH:D012131), AIDS (MESH:D000163), CEP (MESH:C535590), bacterial infection (MESH:D001424), invasive aspergillosis (MESH:D055744), bleeding disorders (MESH:D006470), infiltrates (MESH:D017254), hypersensitivity pneumonitis (MESH:D000542), CMV (MESH:D003586), RP (MESH:D012174)
- **Chemicals:** fatty acid (MESH:D005227), Galactomannan (MESH:C012990), amino (-), curcumin (MESH:D003474), linoleic acid (MESH:D019787), HE (MESH:D006371), spermidine (MESH:D013095), lipids (MESH:D008055), spermine (MESH:D013096), alpha-linolenic acid (MESH:D017962)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mycobacterium tuberculosis (species) [taxon 1773], Streptococcus (genus) [taxon 1301], Pseudomonadota (proteobacteria, phylum) [taxon 1224]

## Full text

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## Figures

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## References

88 references — full list in the complete paper: https://tomesphere.com/paper/PMC12957099/full.md

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Source: https://tomesphere.com/paper/PMC12957099