Development of new treatment for DLBCL through the analysis of microenvironment in combination with genomic alteration

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08818
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyushu University
• Principal Investigator: Koji Kato 九州大学, 大学病院, 講師 (20571764)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 悪性リンパ腫 / ゲノム変異 / 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. Several prognostic models have been established by focusing primarily on characteristics of lymphoma cells. However, the prognostic impact of the lymphoma microenvironment and its association with characteristics of lymphoma cells are not fully understood. The presence of normal germinal center (GC)-microenvironmental cells, including follicular T cells, macrophage/dendritic cells, and stromal cells in lymphoma tissue indicates a positive therapeutic response. Our prognostic model clearly identified patients with graded prognosis independently of existing prognostic models. We observed increased incidences of genomic alterations associated with poor prognosis in DLBCL tissues lacking GC-microenvironmental cells. These data suggest that the loss of GC-microenvironmental signature dictates clinical outcomes of DLBCL patients reflecting the accumulation of unfavorable molecular signatures.

Free Research Field

悪性リンパ腫

Academic Significance and Societal Importance of the Research Achievements

現状、DLBCLのリンパ腫細胞のみを標的とする治療開発には、一定の限界があると言わざるを得ない。一方、キメラ抗原受容体T細胞（CAR-T）療法や免疫チェックポイント阻害薬などに代表される免疫治療は、この限界を克服する可能性がある治療として期待されている。今後、これら免疫治療の開発において、その効果を左右する微小環境の理解は必須であり、本研究はその入口となりうる成果と考えられる。