TGFB1 and neoplasm: PD-1 positive B-cells in RS share the characteristics of the widely described regulatory B lymphocytes (Bregs) (110, 111), which interact with PD-L1-expressing immune-cells of the tumor stroma and subsequently with inhibitory cytokines (TGF-β and IL-10) from adjacent TL (Table 1B). Bregs are described as a B lymphocyte subtype representing less than 10% of total B-cells in a healthy patient but essential for the maintenance of immunotolerance (111).