Eludation of organ tropism from the diversity of malignant lymphoma and its application to novel treatment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08751
• 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: Nagoya University
• Principal Investigator: Shimada Kazuyuki 名古屋大学, 医学部附属病院, 講師 (50631503)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 悪性リンパ腫 / 微小環境 / がん関連線維芽細胞

Outline of Final Research Achievements

In this study, we elucidated that exosomes from cancer associated fibroblasts (CAFs) derived from nodal lesion of malignant lymphoma elicited anti-pyrimidine drugs resistance such as cytarabine and gemcitabine through modulation of it transporter. In addition, we also elucidated that cytokines secreted from CAFs enhanced antibody dependent cytotoxicity of anti-CD20 monoclonal antibody, while exosomes induced the resistance to HDAC inhibitor. Moreover, we demonstrated the efficacy of anti-PD-1 monoclonal antibody in PD-L1 positive tumor in patient xenograft mouse model established from an intractable intravascular large B-cell lymphoma patient.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

悪性リンパ腫の節性病変を構成するCAFより分泌されるサイトカインやエクソソームが免疫担当細胞の抗体依存性細胞傷害活性の増強、腫瘍細胞の抗がん薬耐性化の獲得など様々な生理作用に関与する可能性を示したことは、悪性リンパ腫の多様性のある病態を理解する一助となり学術的意義があると考えられる。また、難治性悪性リンパ腫患者由来異種移植マウスモデルにおいても抗PD-1抗体医薬の薬効が確認出来たことは、難治性病態に対するPD-L1を標的とする治療応用への可能性に繋がる点で意義深いと考えられる。