Gene alterations and anti-tumor immunity
| Project/Area Number |
17K18388
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
Respiratory organ internal medicine
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Togashi Yosuke 国立研究開発法人国立がん研究センター, 先端医療開発センター, 研究員 (80758326)
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| Research Collaborator |
Tsuboi Masahiro
Shitara Kohei
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | がん免疫 / ゲノム異常 / 非小細胞肺癌 / 体細胞変異数 / EGFR遺伝子変異 / 胃癌 / 腫瘍免疫 / 非小細胞肺がん |
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| Outline of Final Research Achievements |
We investigated immunological phenotypes in tumor microenvironment (TME) of EGFR-mutated lung adenocarcinomas, to which cancer immunotherapy is largely ineffective. While EGFR-mutated lung adenocarcinomas had non-inflamed tumor micronenvironment, CD4+ effector regulatory T cells (Tregs), that are highly infiltrated. The EGFR signal plays an important role in this unique tumor micronenvironment and an EGFR signal inhibitor improved the immune status, and combination with immunotherapy provided better anti-tumor effects compared with either of single treatment.
Furthermore, we investigated gene signature related to Treg-infiltration, showing a specific gene signature. We further analyze this relationship.
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| Academic Significance and Societal Importance of the Research Achievements |
がんの遺伝子異常、特に従来は細胞の増殖や生存に深く関わるとされてきたようなドライバー遺伝子異常が、積極的にがんの周囲の免疫状態をコントロールして、がんにとって有利な環境を作り出していることが明らかとなった。これらの遺伝子異常を標的にするような薬剤とがん免疫療法を併用することで、今までは効果があまりなかった症例に対しても効果を発揮できる可能性がある。
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Report
(3 results)
Research Products
(30 results)
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[Journal Article] Mutational activation of the epidermal growth factor receptor down-regulates major histocompatibility complex class I expression via the extracellular signal-regulated kinase in non-small cell lung cancer.2018
Author(s)
Watanabe S, Hayashi H, Haratani K, Shimizu S, Tanizaki J, Sakai K, Kawakami H, Yonesaka K, Tsurutani J, Togashi Y, Nishio K, Ito A, Nakagawa K.
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Journal Title
Cancer Sci.
Volume: 110(1)
Issue: 1
Pages: 52-60
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical significance of Akt2 in advanced pancreatic cancer treated with erlotinib.2017
Author(s)
Banno E, Togashi Y, de Velasco MA, Mizukami T, Nakamura Y, Terashima M, Sakai K, Fujita Y, Kamata K, Kitano M, Kudo M, Nishio K
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Journal Title
Int J Oncol
Volume: 50
Issue: 6
Pages: 2049-2058
DOI
Related Report
Peer Reviewed
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[Journal Article] Tumor Immune Microenvironment and Nivolumab Efficacy in EGFR Mutation-Positive Non-Small Cell Lung Cancer Based on T790M Status After Disease Progression During EGFR-TKI Treatment2017
Author(s)
K. Haratani, H. Hayashi*, T. Tanaka, H. Kaneda, Y. Togashi, K. Sakai, K. Hayashi, S. Tomida, Y. Chiba, K. Yonesaka, Y. Nonagase, T. Takahama, J. Tanizaki, K. Tanaka, T. Yoshida, K. Tanimura, M. Takeda, H. Yoshioka, T. Ishida, T. Mitsudomi, K. Nishio and K. Nakagawa
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Journal Title
Annals of Oncology
Volume: in press
Issue: 7
Pages: 1532-1539
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Efficacy of irreversible EGFR-TKIs for the uncommon secondary resistant EGFR mutations L747S, D761Y, and T854A.2017
Author(s)
Chiba M, Togashi Y, Bannno E, Kobayashi Y, Nakamura Y, Hayashi H, Terashima M, De Velasco MA, Sakai K, Fujita Y, Mitsudomi T, Nishio K.
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Journal Title
BMC Cancer.
Volume: 17
Issue: 1
Pages: 281-281
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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