Elucidation of mechanisms underlying lymphoproliferative disorders for targeted therapy in patients with autoimmune diseases

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08683
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Hokkaido University
• Principal Investigator: Hatanaka Kanako 北海道大学, 大学病院, 特任講師 (10399834)
• Co-Investigator(Kenkyū-buntansha): 畑中 豊 北海道大学, 大学病院, 特任准教授 (30589924)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: リンパ増殖性疾患 / 自己免疫性疾患 / びまん性大細胞型B細胞リンパ腫 / 腫瘍微小環境

Outline of Final Research Achievements

In this study, we analyzed the tumor microenvironment of diffuse large B-cell lymphoma (DLBCL) in patients with autoimmune disease (AID) treated with immunosuppressants. The number of patients with increased FOXP3-positive regulatory T-cell infiltration was significantly higher in the AID group than in the non-AID (nAID) group. Gene expression profiling revealed a significant difference in 7 genes between AID and nAID groups. In addition, among the 24 differentially expressed genes between the AID group with and without EBV infection, 4 genes including TNFRSF8 (CD30) showed increased expression. These results further our understanding of the tumor microenvironment and can be useful for the development of therapeutic strategies for AID-DLBCL patients in the future.

Free Research Field

人体病理

Academic Significance and Societal Importance of the Research Achievements

本研究ではAID-DLBCLの腫瘍微小環境に着目し、nAID-DLBCLとの比較やEBV感染の有無を含めた解析を行った。腫瘍微小環境の浸潤細胞の密度に大きな差異は認められなかったが、遺伝子発現プロファイル解析では複数の遺伝子発現に違いがみられたことから、形態的は大きな差異のない両者においても腫瘍微小環境に違いがみられることが判明し、かつその中の高発現を示す遺伝子をターゲットにした治療薬がすでに他の腫瘍で臨床導入されていることから、本疾患における新たな治療法の可能性を見出した。