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

• Published in: Pathology, research and practice research and practice, 2024-02, Vol.254, p.155117-155117, Article 155117
• Main Authors: Mishina, Tatsuzo, Miyoshi, Hiroaki, Takeuchi, Mai, Miyawaki, Kohta, Nakashima, Kazutaka, Yamada, Kyohei, Moritsubo, Mayuko, Inoue-Mitsuyama, Kanako, Shimasaki, Yasumasa, Imamoto, Teppei, Kawamoto, Keisuke, Furuta, Takuya, Kohno, Kei, Kato, Koji, Akashi, Koichi, Ohshima, Koichi
• Format: Article
• Language: English
• Subjects: Diffuse large B-cell lymphoma; IL-10; Immunohistochemistry; nCounter; Regulatory B-cell; TGF-β
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2024.155117

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. [Display omitted]