WCLC 2025 - Posters & ePosters-PT1.06.04 Signatures of Functional CD8 T, Marginal Zone/Memory B and NK Cells in PBMCpredict Survivalin NSCLC Patients Receiving Chemoimmunotherapy

PT1.06.04 Signatures of Functional CD8 T, Marginal Zone/Memory B and NK Cells in PBMCpredict Survivalin NSCLC Patients Receiving Chemoimmunotherapy

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This study investigates peripheral blood mononuclear cells (PBMC)-derived immune signatures as predictors of clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients receiving first-line chemo-immunotherapy. Despite the standard use of chemo-immunotherapy for EGFR/ALK-negative advanced NSCLC, patient responses vary widely. The authors enrolled 133 treatment-naïve advanced NSCLC patients, randomly assigned to a training cohort (Cohort 1, n=81) and a validation cohort (Cohort 2, n=52). Baseline PBMCs were collected before treatment and profiled using bulk RNA sequencing.<br /><br />Using published immune gene sets, the study identified core gene modules corresponding to CD8+ T cells, marginal zone/memory B cells, and natural killer (NK) cells associated with overall survival (OS). Single-cell RNA sequencing from public datasets confirmed the localization of these genes within expected immune subsets. A composite risk score integrating these three cell-type signatures was constructed: Risk score = 0.40 × T cell module + 0.23 × NK cell module + 0.05 × B cell module. This composite score robustly stratified patients by progression-free survival (PFS) and OS in the training set.<br /><br />Importantly, the model’s validity extended to the independent validation cohort and to tumor tissue RNA data from two second-line immune checkpoint inhibitor (ICI) clinical trials, OAK (n=344) and POPLAR (n=81), supporting its generalizability. High composite risk scores consistently predicted worse progression and survival outcomes. The composite score outperformed PD-L1 status in prognostic value.<br /><br />The findings suggest that baseline PBMC immune profiling incorporating functional CD8 T, marginal zone/memory B, and NK cell signatures can stratify advanced NSCLC patients by risk, informing personalized monitoring and therapeutic strategies. The authors recommend prospective multicenter validation, integration with other biomarkers (e.g., ctDNA, PD-L1, radiomics), and evaluating the score’s utility in guiding treatment intensity. This approach highlights the potential of peripheral blood immune signatures as accessible, robust predictors in immuno-oncology.

Asset Subtitle

Jialei Wang

Meta Tag

Speaker Jialei Wang

Topic Pathology and Biomarkers

Keywords

Peripheral blood mononuclear cells

Immune signatures

Advanced non-small cell lung cancer

Chemo-immunotherapy

CD8+ T cells

Natural killer cells

Memory B cells

Risk score

Progression-free survival

Immune checkpoint inhibitors