2021 Fiscal Year Annual Research Report
Association of immune responses with racial differences of cancer development
| Project/Area Number |
17H06162
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| Research Institution | Nagoya University |
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Principal Investigator |
西川 博嘉 名古屋大学, 医学系研究科, 教授 (10444431)
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| Co-Investigator(Kenkyū-buntansha) |
土井 俊彦 国立研究開発法人国立がん研究センター, 東病院, 科長 (20522907)
河野 隆志 国立研究開発法人国立がん研究センター, 研究所, 分野長 (80280783)
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| Project Period (FY) |
2017-05-31 – 2022-03-31
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| Keywords | 発がん / がん免疫 / 腫瘍微小環境 |
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| Outline of Annual Research Achievements |
本研究では、ドライバー遺伝子異常による発がんに人種差が認められる原因が、遺伝子異常が免疫応答に与える影響の差に起因するという仮説に基づき、種々のがん種で見られる遺伝子異常が抗腫瘍免疫応答にもたらす影響を検討した。がん細胞が持つ遺伝子異常がケモカインなどの化学メディエーターの分泌や代謝環境に直接的に影響を与えることで、免疫抑制性の制御性T細胞の浸潤を増強するとともにエフェクターT細胞の浸潤阻害や機能低下を誘導するなどにより腫瘍微小環境を構築し、発がん、がんの進展を促進していることを見出した。つまり、免疫抑制細胞である制御性Ｔ細胞の腫瘍組織への浸潤、活性化を誘導する一方で、エフェクターT細胞の腫瘍組織への浸潤阻害をもたらしていることを解明した。また、肺腺癌リスクにかかわるHLAアレルを同定し、免疫応答誘導、特にT細胞誘導の可否が発がんと関連することを明らかにし、HLA差が発がんの人種差の原因となっている可能性を明らかにした。
がんの進展過程での新たな概念の提唱につながり、がん免疫ゲノム医学として新たな学術分野を創生した。また、遺伝子変異に対する分子標的治療が免疫調節作用をもつことの発見にもつながり、免疫賦活剤としての分子標的治療と免疫治療の融合によるがん免疫ゲノム治療開発に展開された。本研究成果は、現在AMED次世代がん医療加速化研究事業等にも展開され、今後さらに臨床応用が進むと考えられ、「がん撲滅」という社会的ニーズに大きく貢献した。
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| Research Progress Status |
令和3年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
令和3年度が最終年度であるため、記入しない。
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[Journal Article] PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes2022
Author(s)
Nagasaki J, Inozume T, Sax N, Ariyasu R, Ishikawa M, Yamashita K, Kawazu M, Ueno T, Irie T, Tanji E, Morinaga T, Honobe A, Ohnuma T, Yoshino M, Iwata T, Kawase K, Sasaki K, Hanazawa T, Kochin V, Kawamura T, Matsue H, Hino M, Mano H, Suzuki Y, Nishikawa H, Togashi Y
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Journal Title
Cell Reports
Volume: 38
Pages: 110331～110331
DOI
Peer Reviewed / Open Access
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[Journal Article] Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments2022
Author(s)
Kumagai S, Koyama S, Itahashi K, Tanegashima T, Lin YT, Togashi Y, Kamada T, Irie T, Okumura G, Kono H, Ito D, Fujii R, Watanabe S, Sai A, Aokage K, Suzuki J, Ishii G, Kuwata T, Sakamoto N, Kawazu M, Ueno T, Mori T, Yamazaki N, Tsuboi M, Yatabe Y, Kinoshita T, Doi T, Shitara K, Mano H, Nishikawa H
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Journal Title
Cancer Cell
Volume: 40
Pages: 201～218.e9
DOI
Peer Reviewed
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[Journal Article] HLA Class I Analysis Provides Insight Into the Genetic and Epigenetic Background of Immune Evasion in Colorectal Cancer With High Microsatellite Instability2022
Author(s)
Kawazu M, Ueno T, Saeki K, Sax N, Togashi Y, Kanaseki T, Chida K, Kishigami F, Sato K, Kojima S, Tanegashima T, Matsubara D, Tane K, Tanaka Y, Iinuma H, Hashiguchi Y, Hazama S, Khor SS, Tokunaga K, Tsuboi M, Niki T, Eto M, Shitara K, Torigoe T, Ishihara S, Aburatani H, Haeno H, Nishikawa H, Mano H
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Journal Title
Gastroenterology
Volume: 162
Pages: 799～812
DOI
Peer Reviewed
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[Journal Article] A multicenter, open-label, single-arm phase I trial of neoadjuvant nivolumab monotherapy for resectable gastric cancer2022
Author(s)
Hasegawa H, Shitara K, Takiguchi S, Takiguchi N, Ito S, Kochi M, Horinouchi H, Kinoshita T, Yoshikawa T, Muro K, Nishikawa H, Suna H, Kodera Y
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Journal Title
Gastric Cancer
Volume: －
Pages: －
DOI
Peer Reviewed
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[Journal Article] Preoperative Chemoradiotherapy Plus Nivolumab Before Surgery in Microsatellite Stable and Microsatellite Instability-High Locally Advanced Rectal Cancer Patients2022
Author(s)
Bando H, Tsukada Y, Inamori K, Togashi Y, Koyama S, Kotani D, Fukuoka S, Yuki S, Komatsu Y, Homma S, Taketomi A, Uemura M, Kato T, Fukui M, Wakabayashi M, Nakamura N, Kojima M, Kawachi H, Kirsch R, Yoshida T, Suzuki Y, Sato A, Nishikawa H, Ito M, Yoshino T
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Journal Title
Clinical Cancer Research
Volume: 28
Pages: 1136～1146
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade2022
Author(s)
Miyai Y, Sugiyama D, Hase T, Asai N, Taki T, Nishida K, Fukui T, Chen-Yoshikawa TF, Kobayashi H, Mii S, Shiraki Y, Hasegawa Y, Nishikawa H, Ando Y, Takahashi M, Enomoto A
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Journal Title
Life Science Alliance
Volume: 5
Pages: e202101230
DOI
Peer Reviewed / Open Access
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[Journal Article] Anti-pituitary antibodies and susceptible human leukocyte antigen alleles as predictive biomarkers for pituitary dysfunction induced by immune checkpoint inhibitors2021
Author(s)
Kobayashi T, Iwama S, Sugiyama D, Yasuda Y, Okuji T, Ito M, Ito S, Sugiyama M, Onoue T, Takagi H, Hagiwara D, Ito Y, Suga H, Banno R, Nishikawa H, Arima H
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Journal Title
Journal for ImmunoTherapy of Cancer
Volume: 9
Pages: e002493～e002493
DOI
Peer Reviewed / Open Access
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[Journal Article] Importance of lymph node immune responses in MSI-H/dMMR colorectal cancer2021
Author(s)
Inamori K, Togashi Y, Fukuoka S, Akagi K, Ogasawara K, Irie T, Motooka D, Kobayashi Y, Sugiyama D, Kojima M, Shiiya N, Nakamura S, Maruyama S, Suzuki Y, Ito M, Nishikawa H
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Journal Title
JCI Insight
Volume: 6
Pages: －
DOI
Peer Reviewed / Open Access
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[Journal Article] CD4+T cells are essential for the development of destructive thyroiditis induced by anti-PD-1 antibody in thyroglobulin-immunized mice2021
Author(s)
Yasuda Y, Iwama S, Sugiyama D, Okuji T, Kobayashi T, Ito M, Okada N, Enomoto A, Ito S, Yan Y, Sugiyama M, Onoue T, Tsunekawa T, Ito Y, Takagi H, Hagiwara D, Goto M, Suga H, Banno R, Takahashi M, Nishikawa H, Arima H
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Journal Title
Science Translational Medicine
Volume: 13
Pages: －
DOI
Peer Reviewed
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[Journal Article] Adult-Onset Anti-Citrullinated Peptide Antibody-Negative Destructive Rheumatoid Arthritis Is Characterized by a Disease-Specific CD8+ T Lymphocyte Signature2021
Author(s)
Kelkka T, Savola P, Bhattacharya D, Huuhtanen J, Lonnberg T, Kankainen M, Paalanen K, Tyster M, Lepisto M, Ellonen P, Smolander J, Eldfors S, Yadav B, Khan S, Koivuniemi R, Sjowall C, Elo LL, Lahdesmaki H, Maeda Y, Nishikawa H, Leirisalo-Repo M, Sokka-Isler T, Mustjoki S
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Journal Title
Frontiers in Immunology
Volume: 12
Pages: －
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells2021
Author(s)
Satoh K, Kobayashi Y, Fujimaki K, Hayashi S, Ishida S, Sugiyama D, Sato T, Lim K, Miyamoto M, Kozuma S, Kadokura M, Wakita K, Hata M, Hirahara K, Amano M, Watanabe I, Okamoto A, Tuettenberg A, Jonuleit H, Tanemura A, Maruyama S, Agatsuma T, Wada T, Nishikawa H
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Journal Title
International Immunology
Volume: 33
Pages: 435～446
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Vescimonas gen. nov., Vescimonas coprocola sp. nov., Vescimonas fastidiosa sp. nov., Pusillimonas gen. nov. and Pusillimonas faecalis sp. nov. isolated from human faeces2021
Author(s)
Kitahara M, Shigeno Y, Shime M, Matsumoto Y, Nakamura S, Motooka D, Fukuoka S, Nishikawa H, Benno Y
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Journal Title
International Journal of Systematic and Evolutionary Microbiology
Volume: 71
Pages: －
DOI
Peer Reviewed
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[Journal Article] TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment2021
Author(s)
Kawashima S, Inozume T, Kawazu M, Ueno T, Nagasaki J, Tanji E, Honobe A, Ohnuma T, Kawamura T, Umeda Y, Nakamura Y, Kawasaki T, Kiniwa Y, Yamasaki O, Fukushima S, Ikehara Y, Mano H, Suzuki Y, Nishikawa H, Matsue H, Togashi Y
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Journal Title
Journal for ImmunoTherapy of Cancer
Volume: 9
Pages: e003134～e003134
DOI
Peer Reviewed / Open Access
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[Journal Article] Highly immunogenic cancer cells require activation of the WNT pathway for immunological escape2021
Author(s)
Takeuchi Y, Tanegashima T, Sato E, Irie T, Sai A, Itahashi K, Kumagai S, Tada Y, Togashi Y, Koyama S, Akbay EA, Karasaki T, Kataoka K, Funaki S, Shintani Y, Nagatomo I, Kida H, Ishii G, Miyoshi T, Aokage K, Kakimi K, Ogawa S, Okumura M, Eto M, Kumanogoh A, Tsuboi M, Nishikawa H
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Journal Title
Science Immunology
Volume: 6
Pages: －
DOI
Peer Reviewed
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[Journal Article] Regulatory T Cell as a Biomarker of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia2021
Author(s)
Fujioka Y, Sugiyama D, Matsumura I, Minami Y, Miura M, Atsuta Y, Ohtake S, Kiyoi H, Miyazaki Y, Nishikawa H, Takahashi N
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Journal Title
Cancers
Volume: 13
Pages: 5904～5904
DOI
Peer Reviewed / Open Access
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[Journal Article] Depletion of central memory CD8+ T cells might impede the antitumor therapeutic effect of Mogamulizumab2021
Author(s)
Maeda Y, Wada H, Sugiyama D, Saito T, Irie T, Itahashi K, Minoura K, Suzuki S, Kojima T, Kakimi K, Nakajima J, Funakoshi T, Iida S, Oka M, Shimamura T, Doi T, Doki Y, Nakayama E, Ueda R, Nishikawa H
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Journal Title
Nature Communications
Volume: 12
Pages: －
DOI
Peer Reviewed / Open Access
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[Journal Article] TAS-116 (Pimitespib), an Oral HSP90 Inhibitor, in Combination with Nivolumab in Patients with Colorectal Cancer and Other Solid Tumors: An Open-Label, Dose-Finding, and Expansion Phase Ib Trial (EPOC1704)2021
Author(s)
Kawazoe A, Itahashi K, Yamamoto N, Kotani D, Kuboki Y, Taniguchi H, Harano K, Naito Y, Suzuki M, Fukutani M, Higuchi T, Ikeno T, Wakabayashi M, Sato A, Koyama S, Nishikawa H, Shitara K
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Journal Title
Clinical Cancer Research
Volume: 27
Pages: 6709～6715
DOI
Peer Reviewed
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[Presentation] Preoperative Chemoradiotherapy plus Consolidation Immune-Checkpoint Inhibitor followed by Radical Surgery for Locally Advanced Rectal Cancer2021
Author(s)
Tsukada Y, Bando H, Inamori K, Togashi Y, Koyama S, Kotani D, Fukuoka S, Yuki S, Komatsu Y, Homma S, Taketomi A, Uemura M, Kato T, Fukui M, Wakabayashi M, Nakamura N, Kojima M, Sato A, Nishikawa H, Ito M, Yoshino T
Organizer
第59回日本癌治療学会学術集会
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[Presentation] Novel concept of EGFR-signal contribution to unique immunological status in EGFR-mutated NSCLC2021
Author(s)
Sugiyama E, Togashi Y, Takeuchi Y, Shinya S, Tada Y, Kataoka K, Tane K, Sato E, Ishii G, Goto K, Shinntani Y, Okumura M, Tsuboi M, Nishikawa H
Organizer
第80回日本癌学会学術総会
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[Presentation] Prediction of tumor microenvironment using Oxygen saturation endoscopic imaging2021
Author(s)
Sato D, Koyama S, Kumagai S, Sai A, Sunakawa H, Kotani D, Kawazoe A, Sakashita S, Yoda Y, Shitara K, Kuwata T, Nishikawa H, Yano T
Organizer
第80回日本癌学会学術総会
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[Presentation] Novel anti-GARP antibody DS-1055a depletes highly suppressive GARP+ regulatory T cells and augments anti-tumor immunity2021
Author(s)
Teiji Wada, Kazuki Satoh, Yoichi Kobayashi, Kaori Fujimaki, Shinko Hayashi, Saori Ishida, Daisuke Sugiyama, Masato Hata, Kazuki Hirahara, Masato Amano, Ichiro Watanabe, Atsushi Okamoto, Atsushi Tanemura, Shoichi Maruyama, Toshinori Agatsuma, Hiroyoshi Nishikawa
Organizer
The 29th Annual Meeting of The Korean Society of Applied Pharmacology
Int'l Joint Research
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[Presentation] ANTI-COX-2 AUTOANTIBODY AS A NOVEL DIAGNOSTIC MARKER IN APLASTIC ANEMIA2021
Author(s)
Kelkka T, Tyster M, Lundgren S, Kerr C, Hosokawa K, Huuhtanen J, Keranen M, Feng X, Kawakami T, Maeda Y, Nieminen O, Kasanen T, Aronen P, Yadav B, Rajala H, Nakazawa H, Jaatinen T, Ogawa S, Ishida F, Nishikawa H, Young N, Nakao S, Maciejewski J, Mustjoki S
Organizer
European Hematology Association Congress 2021(EHA2021)
Int'l Joint Research
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[Presentation] Neoadjuvant Nivolumab Monotherapy in Patients With Resectable Gastric Cancer: Preliminary Results From a Multicenter Study2021
Author(s)
Takiguchi S, Shitara K, Takiguchi N, Ito S, Kochi M, Horinouchi H, Kinoshita T, Muro K, Yoshikawa T, Hasegawa H, Nishikawa H, Kodera Y
Organizer
2021 ASCO Annual Meeting
Int'l Joint Research
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[Presentation] Dissecting Transcriptomic Heterogeneity In Primary Esophageal Squamous Cell Carcinoma By Single-Cell RNA Sequencing2021
Author(s)
Minamide T, Kashima Y, Irie T, Koyama S, Togashi Y, Suzuki, A, Yamashita H, Nakamura Y, Shitara K, Tanaka H, Yoshida T, Inaki K, Chihara M, Wada T, Nishimura K, Nakamura A, Murai S, Ohashi A, Suzuki Y, Tsuchihara K, Nishikawa H, Yano T, Doi T
Organizer
Digestive Disease Week (DDW) 2021
Int'l Joint Research
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