Overexpression of interleukin-20 correlates with favourable prognosis in diffuse large B-cell lymphoma

Yi-Sian Lu; Po-Min Chiang; Yi-Ching Huang; Shiang-Jie Yang; Liang-Yi Hung; L Jeffrey Medeiros; Ya-Ping Chen; Tsai-Yun Chen; Ming-Shi Chang; Kung-Chao Chang

doi:10.1016/j.pathol.2022.07.007

Overexpression of interleukin-20 correlates with favourable prognosis in diffuse large B-cell lymphoma

Pathology. 2023 Feb;55(1):94-103. doi: 10.1016/j.pathol.2022.07.007. Epub 2022 Sep 6.

Authors

Affiliations

¹ Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁴ Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
⁵ Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁷ Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: changkc@mail.ncku.edu.tw.

PMID: 36175183
DOI: 10.1016/j.pathol.2022.07.007

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma worldwide, accounting for about 40% of cases. The role of cytokines in the pathogenesis of lymphomas has been rarely addressed, although cytokines have a close immunological relationship with lymphocytes. We observed overexpression of interleukin (IL)-20 in reactive germinal centres (GCs) leading us to hypothesise that IL-20 may play a role in lymphomagenesis. In this study, we surveyed for IL-20 expression in various types of lymphoma and found that IL-20 was expressed most frequently in follicular lymphoma (94%), but also in Burkitt lymphoma (81%), mantle cell lymphoma (57%), nodal marginal zone lymphoma (56%), Hodgkin lymphomas (50%), small lymphocytic lymphoma (50%) and diffuse large B-cell lymphoma (DLBCL, 48%). IL-20 was not expressed in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), lymphoplasmacytic lymphoma, and plasmacytoma. T-cell lymphomas were largely negative for IL-20 expression, except for anaplastic large cell lymphoma (ALCL, 61%), which frequently expressed IL-20, especially in cutaneous ALCL, and showed an inverse association with ALK expression (p=0.024). We further tested IL-20 expression in another large cohort of DLBCL and found IL-20 expression more frequently in germinal centre B-cell (GCB) than in non-GCB subtype [16/26 (62%) versus 24/64 (38%), p=0.038]. In this cohort, IL-20 was associated with a lower rate of extranodal involvement (p=0.009), bone marrow involvement (p=0.040), and better overall survival (p=0.020). Mechanistically, IL-20 overexpression promoted G1 cell cycle arrest and subsequent apoptosis of DLBCL cells and vice versa in vitro. We conclude that IL-20 may be involved in lymphomagenesis and may be useful as a prognostic marker in patients with DLBCL. In addition, IL-20 plays an inhibitory role in DLBCL growth, probably through cell cycle regulation.

Keywords: Diffuse large B-cell lymphoma; IL-20; cell cycle regulation; cytokine; favourable prognosis; immunohistochemistry.

MeSH terms

Adult
Cytokines
Humans
Interleukins
Lymphoma, B-Cell, Marginal Zone* / pathology
Lymphoma, Large B-Cell, Diffuse* / metabolism
Prognosis

Substances

Cytokines
Interleukins
interleukin 20