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, = 0.003; and HR = 0.57, = 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.