{Reference Type}: Journal Article
{Title}: Co-expression of regulatory B-cell markers, transforming growth factor β and interleukin-10 as a prognostic factor in diffuse large B-cell lymphoma.
{Author}: Mishina T;Miyoshi H;Takeuchi M;Miyawaki K;Nakashima K;Yamada K;Moritsubo M;Inoue-Mitsuyama K;Shimasaki Y;Imamoto T;Kawamoto K;Furuta T;Kohno K;Kato K;Akashi K;Ohshima K;
{Journal}: Pathol Res Pract
{Volume}: 254
{Issue}: 0
{Year}: 2024 Feb 10
{Factor}: 3.309
{DOI}: 10.1016/j.prp.2024.155117
{Abstract}: Regulatory B cells (Bregs) suppress antitumor immunity by producing anti-inflammatory cytokines such as transforming growth factor β (TGF-β) 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-β and IL-10 expression in tumor biopsy samples using immunohistochemical staining and retrospectively analyzed their clinicopathological characteristics. Fifteen cases (12.2 %) classified as Breg-type DLBCL were positive for both TGF-β 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, Breg-type 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-β 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.