Association of BAL Fluid T-Cell Immune Activity With Tumor PD-L1 Expression and Its Prognostic Value: A Prospective Observational Study

NCT07331701 | Not Yet Recruiting

• 1 other identifier: BRMH 30-2025-48
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective observational study aims to evaluate whether immune profiles of T-cell subsets in bronchoalveolar lavage fluid can complement tumor PD-L1 expression, assessed by immunohistochemistry in tumor tissue specimens, in predicting clinical outcomes in patients with advanced lung cancer. Although tumor PD-L1 expression measured on tissue biopsies is widely used to guide immunotherapy decisions, its predictive value is limited by spatial heterogeneity and sampling variability. By analyzing activated, exhausted, and regulatory T-cell populations in bronchoalveolar lavage fluid and examining their association with tissue-based tumor PD-L1 expression, this study seeks to determine whether combining local immune biomarkers with PD-L1 expression improves the prediction of treatment response and survival in patients receiving standard-of-care systemic therapy.

Conditions

Lung Neoplasms; Tumor Immune Microenvironment

Keywords

Bronchoalveolar Lavage Fluid; Tumor-Infiltrating T Lymphocytes; Programmed Cell Death 1 Ligand 1; Immune Checkpoint Inhibitors; Flow Cytometry; Tumor Immune Microenvironment; Treatment Response; Progression-Free Survival; Overall Survival; Predictive Biomarkers

Outcome Measures

Primary Outcomes (1)

• Correlation Between Bronchoalveolar Lavage T-cell Immunophenotypes and Tumor PD-L1 Expression

  The primary outcome is the association between T-cell immunophenotypes quantified in bronchoalveolar lavage fluid by multicolor flow cytometry and tumor PD-L1 expression assessed by immunohistochemistry. T-cell subsets include activated, exhausted, and regulatory T-cell populations defined by surface marker expression (e.g., PD-1, TIM-3, CD39, CD28, CD25, and CD127). Tumor PD-L1 expression is evaluated as the percentage of PD-L1-positive tumor cells and analyzed as a continuous variable and by predefined categories (\<1%, 1-49%, ≥50%).

  At baseline, prior to initiation of systemic anticancer therapy

Secondary Outcomes (4)

• Differences in Bronchoalveolar Lavage T-cell Immunophenotypes Across Tumor PD-L1 Expression Categories

  At baseline, prior to initiation of systemic anticancer therapy

• Objective Response Rate by Combined Tumor PD-L1 Expression and Bronchoalveolar Lavage T-cell Immunophenotypes

  From treatment initiation to first radiologic response assessment (typically 6-12 weeks)

• Progression-Free Survival by Combined Tumor PD-L1 Expression and Bronchoalveolar Lavage T-cell Immunophenotypes

  From treatment initiation to disease progression or death, up to approximately 24 months

• Overall Survival by Combined Tumor PD-L1 Expression and Bronchoalveolar Lavage T-cell Immunophenotypes

  From treatment initiation to death from any cause, up to approximately 24 months

Study Arms (1)

Advanced Lung Cancer Cohort

Adults with suspected or confirmed stage IV lung cancer undergoing clinically indicated bronchoscopy with bronchoalveolar lavage. Participants are enrolled prospectively as a single observational cohort, and no treatment assignment or intervention is determined by the study. Bronchoalveolar lavage fluid is collected for immune profiling by flow cytometry, and study analyses stratify participants post hoc according to tumor PD-L1 expression levels and bronchoalveolar lavage T-cell immunophenotypes.

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population comprises adult patients evaluated at SMG-SNU Boramae Medical Center in Seoul, Republic of Korea. Participants are drawn from routine clinical practice and include patients undergoing clinically indicated bronchoscopy as part of the diagnostic evaluation or management of suspected or confirmed stage IV lung cancer. All clinical assessments, treatments, and follow-up are performed according to standard-of-care practice based on current clinical guidelines, and no additional diagnostic or therapeutic procedures are introduced solely for research purposes.

You may qualify if:

• Adults aged 19 years or older
• Patients with suspected or histologically confirmed stage IV lung cancer based on clinical and radiologic findings
• Scheduled to undergo clinically indicated bronchoscopy with bronchoalveolar lavage as part of routine clinical care
• Able and willing to provide written informed consent

You may not qualify if:

• Receipt of treatment for acute lower respiratory tract infection (including pneumonia or fungal infection) within 4 weeks prior to bronchoscopy
• History of solid organ transplantation or hematopoietic stem cell transplantation
• Current use of systemic immunosuppressive therapy
• Current or planned use of biologic immunomodulatory agents
• Known autoimmune disease requiring systemic immunosuppressive treatment
• Pregnant women
• Patients with recurrent stage IV lung cancer after prior definitive therapy

Sponsors & Collaborators

• Seoul National University Hospital: lead
• SMG-SNU Boramae Medical Center: collaborator

Study Sites (1)

SMG-SNU Boramae Medical Center

Seoul, Dongjak-gu, 07061, South Korea

Location

Related Publications (7)

• Kim IA, Hur JY, Kim HJ, Kim WS, Lee KY. Extracellular Vesicle-Based Bronchoalveolar Lavage Fluid Liquid Biopsy for EGFR Mutation Testing in Advanced Non-Squamous NSCLC. Cancers (Basel). 2022 May 31;14(11):2744. doi: 10.3390/cancers14112744.

  PMID: 35681723 RESULT

• Kalkanis A, Papadopoulos D, Testelmans D, Kopitopoulou A, Boeykens E, Wauters E. Bronchoalveolar Lavage Fluid-Isolated Biomarkers for the Diagnostic and Prognostic Assessment of Lung Cancer. Diagnostics (Basel). 2022 Nov 25;12(12):2949. doi: 10.3390/diagnostics12122949.

  PMID: 36552956 RESULT

• Masuhiro K, Tamiya M, Fujimoto K, Koyama S, Naito Y, Osa A, Hirai T, Suzuki H, Okamoto N, Shiroyama T, Nishino K, Adachi Y, Nii T, Kinugasa-Katayama Y, Kajihara A, Morita T, Imoto S, Uematsu S, Irie T, Okuzaki D, Aoshi T, Takeda Y, Kumagai T, Hirashima T, Kumanogoh A. Bronchoalveolar lavage fluid reveals factors contributing to the efficacy of PD-1 blockade in lung cancer. JCI Insight. 2022 May 9;7(9):e157915. doi: 10.1172/jci.insight.157915.

  PMID: 35389889 RESULT

• Mariniello A, Tabbo F, Indellicati D, Tesauro M, Rezmives NA, Reale ML, Listi A, Capelletto E, Carnio S, Bertaglia V, Mecca C, Consito L, De Filippis M, Bungaro M, Paratore C, Di Maio M, Passiglia F, Righi L, Sangiolo D, Novello S, Geuna M, Bironzo P. Comparing T Cell Subsets in Broncho-Alveolar Lavage (BAL) and Peripheral Blood in Patients with Advanced Lung Cancer. Cells. 2022 Oct 14;11(20):3226. doi: 10.3390/cells11203226.

  PMID: 36291098 RESULT

• Mansour MSI, Hejny K, Johansson F, Mufti J, Vidis A, Mager U, Dejmek A, Seidal T, Brunnstrom H. Factors Influencing Concordance of PD-L1 Expression between Biopsies and Cytological Specimens in Non-Small Cell Lung Cancer. Diagnostics (Basel). 2021 Oct 18;11(10):1927. doi: 10.3390/diagnostics11101927.

  PMID: 34679625 RESULT

• Ben Dori S, Aizic A, Sabo E, Hershkovitz D. Spatial heterogeneity of PD-L1 expression and the risk for misclassification of PD-L1 immunohistochemistry in non-small cell lung cancer. Lung Cancer. 2020 Sep;147:91-98. doi: 10.1016/j.lungcan.2020.07.012. Epub 2020 Jul 13.

  PMID: 32683207 RESULT

• Gniadek TJ, Li QK, Tully E, Chatterjee S, Nimmagadda S, Gabrielson E. Heterogeneous expression of PD-L1 in pulmonary squamous cell carcinoma and adenocarcinoma: implications for assessment by small biopsy. Mod Pathol. 2017 Apr;30(4):530-538. doi: 10.1038/modpathol.2016.213. Epub 2017 Jan 6.

  PMID: 28059094 RESULT

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Deog Kyeom Kim, MD, PhD

CONTACT

+82-2-870-2228; kimdkmd@gmail.com

Heemoon Park, MD

CONTACT

+82-2-870-3439; coramdeo33@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Pulmonary and Critical Care Medicine, SMG-SNU Boramae Medical Center

Study Record Dates

• First Submitted: December 29, 2025
• First Posted: January 12, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 12, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)