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B Cell dysfunction in tumor-draining lymph nodes predicts relapse in oral squamous cell carcinoma

Vilma Liljeström,Pedro Farrajota Neves da Silva,Rusana Bark,A. Elliot,L. Marklund,G. Margolin,S. Kumlien Georén,L. Cardell,Krzysztof Piersiala

Published 2025 in Cancer Immunology and Immunotherapy

ABSTRACT

Oral squamous cell carcinoma (OSCC) presents a persistent clinical challenge, with high recurrence rates and limited improvements in survival despite therapeutic advances. Tumor-draining lymph nodes (TDLNs) are key immunological sites where anti-tumor responses are orchestrated, yet the prognostic relevance of B cell phenotypes in TDLNs remains underexplored. TDLNs from 49 OSCC patients treated at Karolinska University Hospital were prospectively analyzed. Single-cell suspensions were examined using multicolor flow cytometry to characterize B cell subsets (naïve, memory, plasma cells) and expression of immunoregulatory markers (CD11c, CD24, CXCR5, CD73, HLA-DR, PD-L1). B cell profiles were correlated with clinical outcomes, including disease-free survival (DFS) and overall survival (OS). Disease-free patients exhibited a distinct B cell profile marked by a higher proportion of naïve B cells, strong CXCR5 and CD11c expression, and increased plasma cell differentiation. Recurrence was associated with elevated CD24, CD73, and HLA-DR expression, markers linked to immunoregulatory or dysfunctional B cell states. Interestingly, high PD-L1 expression on memory B cells correlated with improved prognosis, suggesting a context-dependent immune function. In line with these observations, multivariate analysis confirmed HLA-DR expression, together with nodal status, as independent prognostic factors for survival in OSCC. B cell phenotypes in OSCC TDLNs are strongly associated with patient outcomes. A microenvironment enriched in naïve and functionally active B cells supports durable tumor control, whereas regulatory/exhausted phenotypes are linked to recurrence. These findings position B cell markers as promising prognostic indicators and therapeutic targets in OSCC, warranting validation in larger cohorts and functional studies.

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