Association of BAL Fluid T-Cell Immune Activity With Tumor PD-L1 Expression and Its Prognostic Value: A Prospective Observational Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Correlation Between Bronchoalveolar Lavage T-cell Immunophenotypes and Tumor PD-L1 Expression
研究概览
简要总结
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.
详细描述
Tumor PD-L1 expression assessed by immunohistochemistry on tumor tissue specimens is an established biomarker for selecting immune checkpoint inhibitor therapy in lung cancer; however, its clinical utility is limited by intratumoral heterogeneity, temporal variability, and dependence on the size and location of tissue biopsy samples. As a result, tissue-based PD-L1 expression alone does not fully capture the immune context of the tumor microenvironment or reliably predict treatment response and prognosis in all patients.
Bronchoalveolar lavage fluid provides access to the local pulmonary immune microenvironment and contains immune cells that may reflect tumor-immune interactions more directly than peripheral blood. Prior studies suggest that T-cell populations in bronchoalveolar lavage fluid share phenotypic characteristics with tumor-infiltrating lymphocytes and may serve as surrogate indicators of local antitumor immune activity. However, the relationship between bronchoalveolar lavage T-cell immunophenotypes, tissue-based tumor PD-L1 expression, and clinical outcomes has not been comprehensively evaluated in a prospective setting.
This single-center prospective observational cohort study enrolls adult patients with suspected or confirmed stage IV lung cancer who are undergoing clinically indicated bronchoscopy as part of routine diagnostic or management procedures. Residual bronchoalveolar lavage fluid obtained during standard-of-care bronchoscopy is analyzed using multicolor flow cytometry to quantify T-cell subsets, including activated, exhausted, and regulatory populations defined by surface marker expression. Tumor PD-L1 expression is evaluated by immunohistochemistry performed on diagnostic tumor tissue specimens obtained as part of routine clinical care and analyzed both as a continuous variable and by predefined expression categories.
Participants receive standard systemic anticancer therapy according to current clinical guidelines, including immune checkpoint inhibitor-based regimens when indicated. Clinical outcomes, including objective response rate, progression-free survival, and overall survival, are prospectively collected from electronic medical records. The study examines correlations between bronchoalveolar lavage T-cell immunophenotypes and tissue-based tumor PD-L1 expression, as well as whether stratification based on combined immune profiling provides improved prognostic information compared with tumor PD-L1 expression alone.
By integrating local immune profiling from bronchoalveolar lavage fluid with tumor PD-L1 expression assessed in tissue specimens, this study seeks to identify complementary biomarkers that may enhance risk stratification and refine prognostic assessment in advanced lung cancer, potentially informing future approaches to personalized immunotherapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
结局指标
主要结局
Correlation Between Bronchoalveolar Lavage T-cell Immunophenotypes and Tumor PD-L1 Expression
时间窗: At baseline, prior to initiation of systemic anticancer therapy
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%).
次要结局
- 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)
研究者
Deog Kyeom Kim
Professor, Department of Pulmonary and Critical Care Medicine, SMG-SNU Boramae Medical Center
Seoul National University Hospital