Co-expression of regulatory B-cell markers, transforming growth factor and interleukin-10 as a prognostic factor in diffuse large B-cell lymphoma

Regulatory B cells (Bregs) suppress antitumor immunity by producing anti-inflammatory cytokines such as transforming growth factor beta (TGF-beta) and interleukin-10 (IL -10) and promoting tumor growth. It is unknown whether diffuse large B -cell lymphoma (DLBCL), a common subtype of B -cell malignancy, exhibits characteristics similar to those of Bregs. This study aimed to clarify the features of DLBCLs carrying Breg markers. In 123 DLBCL cases, we evaluated TGF-beta and IL -10 expression in tumor biopsy samples using immunohistochemical staining and retrospectively analyzed their clinicopathological characteristics. Fifteen cases (12.2 %) classified as Bregtype DLBCL were positive for both TGF-beta and IL -10. Breg-type DLBCL is mainly classified as having activated B cell-like cells of origin. Breg-type DLBCL cases showed significantly worse progression -free survival and overall survival (OS) than other DLBCL cases (P = 0.0016 and P = 0.042, respectively). In multivariate analysis, Bregtype DLBCL significantly affected OS (hazard ratio, 3.13; 95 % confidence interval 1.15-8.55; P = 0.025). Gene expression analysis showed that the expression of follicular dendritic cell -associated genes (FCER2, PIK3CD, FOXO1) was downregulated in Breg-type DLBCLs compared to other DLBCLs. These results suggest that the double expression of Breg markers, TGF-beta and IL -10, in tumor cells indicates a poor prognosis in DLBCL patients. Further studies evaluating genomic abnormalities could confirm the characteristics of Breg-type DLBCL.