Monday, 26th of January at 12:00 pm – 12:40 pm
Chairs:
Sara di Biasi
University of Modena and Reggio Emilia
Department of Medical and Surgical Sciences for Children & Adults
via Campi, 287 – 41125 Modena, Italy
Dissecting immunometabolic crosstalk between B Cells and T Cells in NSCLC
B cells have emerged as key components of the tumor microenvironment (TME) in non-small cell lung cancer (NSCLC). Despite increasing evidence supporting their role in antitumor immunity, limited information is available regarding the phenotypic diversity, metabolic features, and functional interactions of B cells with T cells in NSCLC. In this study, we comprehensively characterized B cell populations within the NSCLC TME using polychromatic flow cytometry, mass cytometry, and spatial transcriptomics. Our analyses identified multiple intratumoral B cell clusters exhibiting distinct metabolic and functional properties, including a population of VISTA-expressing regulatory B cells (Bregs). Targeted liquid chromatography–tandem mass spectrometry confirmed VISTA expression on B cells. VISTA⁺ Bregs displayed high bioenergetic demand and produced a broad spectrum of cytokines, including interleukin (IL)-10, transforming growth factor (TGF)-β, IL-6, tumor necrosis factor (TNF), and granulocyte–macrophage colony-stimulating factor (GM-CSF). Spatial transcriptomic analyses revealed close colocalization of B cells with CD4⁺ and CD8⁺ T lymphocytes within the TME. Computational inference of intercellular communication using NicheNet predicted functional B–T cell interactions mediated through the VISTA–PSGL-1 signaling axis. Consistent with these predictions, spatial proximity analyses demonstrated that PSGL-1–expressing T cells are frequently adjacent to VISTA⁺ B cells in tumor tissues. Notably, tumor-infiltrating CD8⁺ T cells expressing PSGL-1 exhibited enhanced metabolic activity. Together, these findings uncover a metabolically active, immunoregulatory B cell compartment in NSCLC and highlight a potential VISTA-mediated mechanism of B–T cell crosstalk within the TME.
Biosketch
Sara De Biasi, a PhD in Clinical and Experimental Medicine (Immunology) from the University of Modena and Reggio Emilia, Italy, holds the position of Assistant Professor of Pathology and Immunology in the lab of Immunology led by Professor Andrea Cossarizza. Her research primarily focuses on the variability of adaptive immune responses observed in patients with COVID-19, HIV, autoimmune diseases, and cancer.
Dr. De Biasi has also been recognized as an International Society for Advancement of Cytometry (ISAC) Marylou Ingram Scholar (2016-2020) and served as a Councilor (2020-2024) for the same Society.