The lymphoma microenvironment is a novel therapeutic target in the treatment of patients with B-cell lymphoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09875
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyushu University
• Principal Investigator: Kato Koji 九州大学, 大学病院, 講師 (20571764)
• Research Collaborator: Miyawaki Kohta ; Sugio Takeshi ; Sasaki Kensuke ; Ohshima Koichi ; Akashi Koichi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 悪性リンパ腫 / 微小環境

Outline of Final Research Achievements

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy with varying prognosis. We assess the clinical impact of the tumor microenvironment on the clinical outcomes and pathophysiological, molecular signatures in DLBCL using transcriptome analysis by nCounter and DNA sequencing. The present study showed that the presence of normal germinal center (GC)-microenvironmental cells, including follicular T, macrophage/dendritic, and stromal cells, in lymphoma tissue is highly associated with better prognosis. Novel prognostic model, based on quantitation of ICOS, CD11c, and FGFR1 transcripts as distinct GC-microenvironmental cell markers, clearly identified patients with graded prognosis. We also found an increased incidence of unfavorable molecular signatures such as poor prognostic genomic alterations or proliferation-related gene expression in DLBCL tissues lacking GC-microenvironmental cells. The specific microenvironmental signature in DLBCL predicts clinical outcomes.

Free Research Field

血液内科

Academic Significance and Societal Importance of the Research Achievements

従来までのDLBCL予後層別化は、B細胞リンパ腫自体の遺伝子プロファイリングが中心で、微小環境との関連について、ほとんど研究されてこなかった。本研究により、リンパ腫微小環境のパターンが、DLBCLの予後をより精確に層別化しうることが分かった。治療開発という側面においても、本研究は、従来行われてきた腫瘍細胞（B細胞）そのものを標的とする治療を革新する次世代の新規治療法の創出に役立つことが期待されうる。