Oncogenesis of the infection- and chronic inflammatory-associated lymphomas and development of novel therapeutic strategy
Project/Area Number |
17K09927
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Kochi University |
Principal Investigator |
DAIBATA Masanori 高知大学, 教育研究部医療学系基礎医学部門, 教授 (50263976)
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Co-Investigator(Kenkyū-buntansha) |
松崎 茂展 高知大学, 医学部, 特任准教授 (00190439)
樋口 智紀 高知大学, 教育研究部医療学系基礎医学部門, 助教 (00448771)
橋田 裕美子 高知大学, 教育研究部医療学系基礎医学部門, 助教 (00767999)
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Project Period (FY) |
2017-04-01 – 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 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 悪性リンパ腫 / ウイルス / 感染症 / 微生物 / 癌 / 炎症 / 感染 |
Outline of Final Research Achievements |
Diffuse large B-cell lymphomas often occur in the setting of longstanding chronic inflammation (DLBCL-CI) and shows association with Epstein-Barr virus (EBV). DLBCL-CI can develop in patients with no predisposing immunodeficiency. This study aimed to investigate the mechanism by which the lymphoma cells escape from the host’s immune evasion. EBV-positive pyothorax-associated lymphoma (PAL) is a prototype of DLBCL-CI and may provide a valuable model for the study of immune evasion by DLBCL-CI. This study demonstrates that PAL cell lines express and produce CCL17 and/or CCL22 chemokines, the ligands of CCR4, in contrast to EBV-negative DLBCL cell lines. PAL cells injected into mice attracted CCR4-expressing Treg cells. The CCR4 antagonist significantly suppressed the recruitment of Treg cells by PAL cells. Furthermore, CCR4-expressing Treg cells were abundantly present in primary PAL tissues. Collectively, these findings provide new insight into the mechanisms of immune evasion by PAL.
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Academic Significance and Societal Importance of the Research Achievements |
Epstein-Barr(EB)ウイルスは成人のほとんどが感染している身近なウイルスであるが、リンパ腫という血液腫瘍も発症させるウイルスである。EBウイルス関連リンパ腫の発症には、ウイルスが人の免疫機構から巧みに逃れていることが予想されているが、その詳細なメカニズムは明らかにされていなかった。 今回の研究は慢性炎症関連EBウイルス陽性リンパ腫の腫瘍免疫回避機構におけるケモカイン系の役割を解明したものである。このような分子を標的にすることにより、難治性の要因となる免疫抑制的な環境を破綻させる効果が期待でき、新たな治療法の開発に向けての基盤データを提供することができた。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Merkel cell polyomavirus and Langerhans cell neoplasm.2018
Author(s)
Murakami I, Wada N, Nakashima J, Iguchi M, Toi M, Hashida Y, Higuchi T, Daibata M, Matsushita M, Iwasaki T, Kuwamoto S, Horie Y, Nagata K, Hayashi K, Oka T, Yoshino T, Imamura T, Morimoto A, Imashuku S, Gogusev J, Jaubert F.
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Journal Title
Cell Commun Signal.
Volume: 16(1)
Issue: 1
Pages: 49-49
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Establishment and characterization of a novel Hodgkin lymphoma cell line, AM-HLH, carrying the Epstein-Barr virus genome integrated into the host chromosome.2017
Author(s)
Masahiko Hayashida, Masanori Daibata, Erika Tagami, Takahiro Taguchi, Fumiyo Maekawa, Katsuhiro Fukutsuka, Takamasa Hayashi, Yoshinori Iwatani, Hitoshi Ohno.
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Journal Title
Hematological Oncology
Volume: 印刷中
Issue: 4
Pages: 567-575
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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