Tumor-Infiltrating CD20⁺ B Lymphocytes: Significance and Prognostic Implications in Oral Cancer Microenvironment

Immunohistochemical analysis of stromal/tumoral CD20⁺ B lymphocytes was performed in 125 OSCC patients. Correlations with immune profiles CD4⁺, CD8⁺, and FOXP3⁺ tumor-infiltrating lymphocytes (TILs), tumoral PD-L1, and stem-related factors NANOG and SOX2 were assessed, and also associations with clinical data and patient survival. There was a strong positive correlation between the infiltration of CD20⁺ B lymphocytes and other immune profiles (i.e., CD4⁺, CD8⁺, and FOXP3⁺ TILs, and CD68⁺ and CD163⁺ macrophages) both in stroma and tumor nests. Strikingly, CD20⁺ TILs were inversely correlated with NANOG/SOX2 expression. Stromal CD20⁺ TILs were significantly associated with T classification and second primary tumors. A stratified survival analysis showed that tumoral CD20⁺ TILs were significantly associated with prognosis in male and younger patients, with tobacco or alcohol consumption, high tumoral CD8⁺ TILs, low tumoral infiltration by CD68⁺ macrophages, positive PD-L1 expression, and negative NANOG/SOX2. Multivariate Cox analysis further revealed clinical stage and tumoral CD20⁺ TILs independently associated with disease-specific survival (HR = 2.42, p = 0.003; and HR = 0.57, p = 0.04, respectively). In conclusion, high CD20⁺ TIL density emerges as an independent good prognostic factor in OSCC, suggesting a role in antitumor immunity. This study also uncovered an inverse correlation between CD20⁺ TILs and CSC marker expression.