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

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.