WCLC 2025 - Posters & ePosters-P3.03.46 Phenotyping Double Negative B Cells in Non-Small Cell Lung Cancer

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This study characterizes double negative (DN) B cells, particularly the DN2 subset, within the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). DN B cells lack IgD and CD27 markers and have been linked to adverse outcomes in NSCLC, though they remain poorly understood. Using multispectral flow cytometry and multiplex immunofluorescence, researchers analyzed B cell subpopulations across peripheral blood mononuclear cells (PBMC), non-cancer lung tissue (NCL), and tumor tissues from NSCLC patients.<br /><br />Findings showed a progressive increase of DN B cells from blood to tumor, with DN cells constituting about 20% of tumor-infiltrating B cells and DN2 cells about 2.3%. DN2 cells localized predominantly within B cell follicles in the TME. Functional analysis revealed DN2 B cells express high levels of the immunosuppressive cytokine IL-10, and DN2 plasmablast-like cells expressed the immune checkpoint ligand PD-L1, both indicative of an immunoregulatory phenotype capable of suppressing T cell responses. tSNE mapping underlined a close relationship between DN2 cells and DN2 plasmablasts.<br /><br />Despite their distinct presence and regulatory characteristics, survival analysis did not find a statistically significant prognostic role for DN2 B cells overall, though there was a negative survival trend observed in squamous cell carcinoma patients with these cells. Future research aims to explore how DN2 B cells may influence other immune populations within the tumor microenvironment, such as cancer-associated fibroblasts.<br /><br />In summary, DN2 B cells are enriched in NSCLC tumors, exhibit immunoregulatory features, and localize to B cell follicles, contributing to the complex immune landscape within NSCLC. While not currently prognostic, their role in modulating tumor immunity warrants further investigation.

Asset Subtitle

Liam Neilson

Meta Tag

Speaker Liam Neilson

Topic Tumor Biology – Translational Biology

Keywords

double negative B cells

DN2 subset

non-small cell lung cancer

tumor microenvironment

immunosuppressive cytokine IL-10

immune checkpoint PD-L1

B cell follicles

immunoregulatory phenotype

tSNE mapping

cancer-associated fibroblasts