Elucidation of mechanisms underlying lymphoproliferative disorders for targeted therapy in patients with autoimmune diseases
| Project/Area Number |
16K08683
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
畑中 豊 北海道大学, 大学病院, 特任准教授 (30589924)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| 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 / 自己免疫性疾患関連リンパ増殖性疾患 / DNAメチル化 / 治療効果予測 / 病理学 / 癌 / ゲノム |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning for mycosis fungoides and Sezary syndrome.2016
Author(s)
Shiratori S, Fujimoto K, Nishimura M, Hatanaka KC, Kosugi-Kanaya M, Okada K, Sugita J, Shigematsu A, Hashimoto D, Endo T, Kondo T, Abe R, Hashino S, Matsuno Y, Shimizu H, Teshima T.
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Journal Title
Hematol Oncol.
Volume: Epub Ahead of Print
Pages: 9-16
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] A pilot study of operational tolerance with a regulatory T cell-based cell therapy in living donor liver transplantation.2016
Author(s)
①Todo S, Yamashita K, Goto R, Zaitsu M, Nagatsu A, Oura T, Watanabe M, Aoyagi T, Suzuki T, Shimamura T, Kamiyama T, Sato N, Sugita J, Hatanaka K, Bashuda H, Habu S, Demetris AJ, Okumura K
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Journal Title
Hepatology
Volume: 00
Pages: 00-00
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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