Analysis of PD-1+ tumor-infiltrating T cells according to cancer antigen hierarchy
Project/Area Number |
20H03694
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 53030:Respiratory medicine-related
|
Research Institution | Okayama University (2021-2022) Chiba Cancer Center (Research Institute) (2020) |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
盛永 敬郎 千葉県がんセンター(研究所), がん治療開発グループ 細胞治療開発研究部, 研究員 (30757000)
|
Project Period (FY) |
2020-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
|
Keywords | 腫瘍免疫 / ネオ抗原 / PD-1 / 制御性T細胞 / がん抗原 / 肺癌 |
Outline of Research at the Start |
抗PD-1/PD-L1抗体はT細胞を活性化しがんに対して効果を発揮している。特に体細胞変異由来のネオ抗原は強い免疫応答を起こすことができるため、それらを認識しているエフェクターT細胞が重要である。申請者は肺癌の臨床検体から腫瘍浸潤T細胞のPD-1発現のバランスが抗PD-1/PD-L1抗体の効果・耐性に関与することを明らかにした。本研究はさらに発展させ、ネオ抗原や共通抗原といった認識するがん抗原の階層性に基づくT細胞のPD-1発現といった表現型や機能の違いを明らかにし、より効果の高い治療や正確なバイオマーカー、個別化細胞療法の基盤データを得ることを目指す。
|
Outline of Final Research Achievements |
Cancer is believed to exist as "cancer" by escaping from antitumor immunity using suppressive molecules and/or suppressive cells such as PD-1/PD-L1 and regulatory T cells (Treg). Since anti-PD-1/PD-L1 antibodies exert their effects by activating the effector capacity of T cells, responders to anti-PD-1/PD-L1 antibodies had high frequency of PD-1+ effector T cells in the tumor microenvironment. Such T cells recognized neoantigens. In contrast, PD-1+ Tregs highly infiltrated in resistant patients. We have shown that suppressiive functuons of PD-1+ Tregs are activated by PD-1 blockade. Furthermore, a specific metabolic environment was involved in PD-1 expression in Tregs.
|
Academic Significance and Societal Importance of the Research Achievements |
腫瘍浸潤PD-1陽性エフェクターT細胞ががん免疫療法の効果に関与し、同時にPD-1陽性Tregが耐性に関与することを明らかにでき、効果予測を正確に行えるようになった。また、新たにPD-1陽性Tregが標的となり得て、そこに代謝環境が関与するため、代謝による制御も新たなコンセプトの治療になり得ると考えられた。これらはがん免疫療法のさらなる治療成績の向上に繋がると考えている。
|
Report
(4 results)
Research Products
(83 results)
-
-
-
-
-
-
-
-
-
[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
-
Journal Title
Gastroenterology
Volume: 162
Issue: 3
Pages: 799-812
DOI
Related Report
Peer Reviewed / Open Access
-
-
[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
-
Journal Title
Clinical Cancer Research
Volume: 28
Issue: 6
Pages: 1136-1146
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[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
-
Journal Title
Cancer Cell
Volume: 40
Issue: 2
Pages: 201-218
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-12021
Author(s)
Koya J, Saito Y, Kameda T, Kogure Y, Yuasa M, Nagasaki J, McClure MB, Shingaki S, Tabata M, Tahira Y, Akizuki K, Kamiunten A, Sekine M, Shide K, Kubuki Y, Hidaka T, Kitanaka A, Nakano N, Utsunomiya A, Togashi Y, Ogawa S, Shimoda K, Kataoka K
-
Journal Title
Blood Cancer Discovery
Volume: 2
Issue: 5
Pages: 450-467
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[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.
-
Journal Title
Journal for ImmunoTherapy of Cancer
Volume: 9
Issue: 11
Pages: e003134-e003134
DOI
NAID
Related Report
Peer Reviewed / Open Access
-
[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
-
Journal Title
Science Immunology
Volume: 6
Issue: 65
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
[Journal Article] Vaginal Transmission of Cancer from Mothers with Cervical Cancer to Infants2021
Author(s)
Arakawa A, Ichikawa H, Kubo T, Motoi N, Kumamoto T, Nakajima M, Yonemori K, Noguchi E, Sunami K, Shiraishi K, Kakishima H, Yoshida H, Hishiki T, Kawakubo N, Kuroda T, Kiyokawa T, Yamada K, Yanaihara N, et al, and Kohno T, Ogawa C.
-
Journal Title
New England Journal of Medicine
Volume: 384
Issue: 1
Pages: 42-50
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies2020
Author(s)
Kumagai S,Togashi Y,Kamada T,Sugiyama E,Nishinakamura H,Takeuchi Y,Vitaly K,Itahashi K,Maeda Y,Matsui S,Shibahara T,Yamashita Y,Irie T,Tsuge A,Fukuoka S,Kawazoe A,Udagawa H,Kirita K,Aokage K,Ishii G,Kuwata T,Nakama K,Kawazu M,Ueno T,Yamazaki N,Goto K,Tsuboi M,Mano H,Doi T,Shitara K,Nishikawa H
-
Journal Title
Nature Immunology
Volume: 21
Issue: 11
Pages: 1346-1358
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Site-Specific and Targeted Therapy Based on Molecular Profiling by Next-Generation Sequencing for Cancer of Unknown Primary Site: A Nonrandomized Phase 2 Clinical Trial2020
Author(s)
Hayashi, H. Takiguchi, Y. Minami, H. Akiyoshi, K. Segawa, Y. Ueda, H. Iwamoto, Y. Kondoh, C. Matsumoto, K. Takahashi, S. Yasui, H. Sawa, T. Onozawa, Y. Chiba, Y. Togashi, Y. Fujita, Y. Sakai, K. Tomida, S. Nishio, K. Nakagawa, K.
-
Journal Title
JAMA Oncol
Volume: 6
Issue: 12
Pages: 1931-1938
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Enhanced Tumor Response to Radiotherapy After PD-1 Blockade in Metastatic Gastric Cancer2020
Author(s)
Sasaki A, Nakamura Y, Togashi Y, Kuno H, Hojo H, Kageyama S, Nakamura N, Takashima K, Kadota T, Yoda Y, Mishima S, Sawada K, Kotani D, Kawazoe A, Kuboki Y, Taniguchi H, Kojima T, Doi T, Yoshino T, Yano T, Kobayashi T, Akimoto T, Nishikawa H, Shitara K.
-
Journal Title
Gastric Cancer
Volume: -
Issue: 5
Pages: 893-903
DOI
NAID
Related Report
Peer Reviewed
-
-
[Journal Article] An Oncogenic Alteration Creates a Microenvironment that Promotes Tumor Progression by Conferring a Metabolic Advantage to Regulatory T Cells2020
Author(s)
Shogo Kumagai, Yosuke Togashi, Chika Sakai, Akihito Kawazoe, Masahito Kawazu, Toshihide Ueno, Eiichi Sato, Takeshi Kuwata, Takahiro Kinoshita, Masami Yamamoto, Sachiyo Nomura, Tetsuya Tsukamoto, Hiroyuki Mano, Kohei Shitara, Hiroyoshi Nishikawa
-
Journal Title
Immunity
Volume: 14
Issue: 1
Pages: 187-203
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
[Journal Article] TENERGY: Multicenter Phase II Study of Atezolizumab Monotherapy Following Definitive Chemoradiotherapy With 5-FU Plus Cisplatin in Patients With Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma2020
Author(s)
Bando H, Kotani D, Tsushima T, Hara H, Kadowaki S, Kato K, Chin K, Yamaguchi K, Kageyama SI, Hojo H, Nakamura M, Tachibana H, Wakabayashi M, Fukutani M, Togashi Y, Fuse N, Nishikawa H, Kojima T.
-
Journal Title
BMC Cancer
Volume: 20
Issue: 1
Pages: 336-336
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] The potential application of PD-1 blockade therapy for early-stage biliary tract cancer.2020
Author(s)
Umemoto K, Togashi Y, Arai Y, Nakamura H, Takahashi S, Tanegashima T, Kato M, Nishikawa T, Sugiyama D, Kojima M, Gotohda N, Kuwata T, Ikeda M, Shibata T, Nishikawa H.
-
Journal Title
Int Immunol.
Volume: 32
Issue: 4
Pages: 273-281
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
[Presentation] 腫瘍微小環境における制御性T細胞に特徴的な代謝学的チェックポイントの同定(Identification of a distinctive metabolic checkpoint of regulatory T cells in the tumor microenvironment)2022
Author(s)
熊谷 尚悟, 小山 正平, 板橋 耕太, 冨樫 庸介, 吉田 達哉, 石井 源一郎, 河津 正人, 山崎 直也, 坪井 正博, 谷田部 恭, 木下 敬弘, 土井 俊彦, 設楽 絋平, 間野 博行, 西川 博嘉
Organizer
第81回日本癌学会学術総会
Related Report
Invited
-
[Presentation] B細胞性リンパ腫におけるPD-L2の生物学的機能と調節機序の解析(Dissecting biological function and regulation of PD-L2 in B-cell lymphoma)2022
Author(s)
新垣 清登, 古屋 淳史, 湯淺 光博, 斎藤 優樹, 田畑 真梨子, Marni McClure, 片山 琴絵, 冨樫 庸介, 井元 清哉, 木暮 泰寛, 片岡 圭亮
Organizer
第63回日本リンパ網内系学会学術集会・総会
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] CD155/TIGIT axisは免疫チェックポイント阻害剤のinflamed resistanceに関与する2021
Author(s)
猪爪 隆史, 川島 秀介, 河津 正人, 池原 譲, 木庭 幸子, 中村 泰大, 梅田 善康, 川崎 朋範, 川村 龍吉, 大沼 毅紘, 保延 亜希子, 冨樫 庸介
Organizer
日本がん免疫学会総会
Related Report
-
[Presentation] 腫瘍局所における代謝機構を介した制御性T細胞の新規PD-1発現機構の解明2021
Author(s)
熊谷 尚悟, 鎌田 貴裕, 冨樫 庸介, 小山 正平, 川添 彬人, 河津 正人, 青景 圭樹, 名嘉眞 健太, 吉田 達哉, 山崎 直也, 大江 裕一郎, 坪井 正博, 設樂 紘平, 間野 博行, 西川 博嘉
Organizer
日本がん免疫学会総会
Related Report
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Phase II Trial of Site-Specific Treatment Based on Gene Expression and Mutation Profiling by next generation sequencing (NGS) for Patients (pts) With Cancer of Unknown Primary Site (CUP)2021
Author(s)
Makoto Arai, Hidetoshi Hayashi, Hironobu Minami, Yuichi Takiguchi, Satomi Watanabe, Masanori Toyoda, Kohei Akiyoshi, Yoshihiko Segawa, Hiroki Ueda, Yasuo Iwamoto, Jun Masuda, Hirohumi Mukai, Toshio Kubo, Yosuke Togashi, Kazuko Sakai, Yoshihiko Fujita, Shuta Tomida, Yasutaka Chiba, Kazuto Nishio, and Kazuhiko Nakagawa
Organizer
第18回日本臨床腫瘍学会学術集会
Related Report
-
[Presentation] The critical role of CD4+ T cells in PD-1 blockade against MHC-II-expressing tumors such as classic Hodgkin lymphoma2021
Author(s)
Joji Nagasaki1, Yosuke Togashi, Takeaki Sugawara, Makiko Itami, Nobuhiko Yamauchi, Junichiro Yuda, Sugano Masato, Ohara Yuuki, Yosuke Minami, Hirohisa Nakamae, Masayuki Hino, Masahiro Takeuchi, Hiroyoshi Nishikawa.
Organizer
第18回日本臨床腫瘍学会学術集会
Related Report
-
-
[Presentation] Efficacy Predictors of Preoperative CRT and Consolidation Nivolumab in Patients with Locally Advanced Rectal Cancer.2021
Author(s)
Koji Inamori, Yosuke Togashi, Hideaki Bando, Yuichiro Tsukada, Shota Fukuoka,Yutaka Suzuki, Daisuke Kotani, Motohiro Kojima, Makoto Fukui, Satoshi Yuki, Yoshito Komatsu, Shigenori Homma, Akinobu Taketomi, Mamoru Uemura, Takeshi Kato, Masaaki Ito, Hiroyoshi Nishikawa, Takayuki Yoshino.
Organizer
第18回日本臨床腫瘍学会学術集会
Related Report
-
-
-
[Presentation] Translational Research of VOLTAGE-A: Efficacy Predictors of Preoperative Chemoradiotherapy and Consolidation Nivolumab in Patients with both Microsatellite Stable and Microsatellite Instability-High Locally Advanced Rectal Cancer2021
Author(s)
Koji Inamori, Yosuke Togashi, Hideaki Bando, Yuichiro Tsukada, Shota Fukuoka, Ayako Suzuki, Yutaka Suzuki, Daisuke Kotani, Motohiro Kojima, Makoto Fukui, Satoshi Yuki, Yoshito Komatsu, Shigenori Homma, Akinobu Taketomi, Mamoru Uemura, Takeshi Kato, Masaaki Ito, Hiroyoshi Nishikawa, Takayuki Yoshino.
Organizer
ASCO-GI2021
Related Report
-
-
-
-
-
-
-
-
[Presentation] Translational research of voltage-A1: Efficacy predictors of preoperative chemoradiotherapy and subsequent nivolumab monotherapy in patients with microsatellite-stable locally advanced rectal cancer.2020
Author(s)
Koji Inamori, Yosuke Togashi, Hideaki Bando, Yuichiro Tsukada, Shota Fukuoka, Ayako Suzuki, Yutaka Suzuki, Daisuke Kotani, Motohiro Kojima, Makoto Fukui, Satoshi Yuki, Yoshito Komatsu, Shigenori Homma, Akinobu Taketomi, Mamoru Uemura, Takeshi Kato, Masaaki Ito, Hiroyoshi Nishikawa, Takayuki Yoshino
Organizer
ASCO2020
Related Report
Int'l Joint Research
-
[Presentation] Short-Term Results of VOLTAGE-A: Nivolumab Monotherapy and Subsequent Radical Surgery Following Preoperative Chemoradiotherapy in Patients with Microsatellite Stable and Microsatellite Instability-High Locally Advanced Rectal Cancer.2020
Author(s)
Satoshi Yuki, Hideaki Bando, Yuichiro Tsukada, Koji Inamori, Yoshito Komatsu, Shigenori Homma, Mamoru Uemura, Takeshi Kato, Daisuke Kotani, Shota Fukuoka, Naoki Nakamura, Makoto Fukui, Masashi Wakabayashi, Motohiro Kojima, Yosuke Togashi, Akihiro Sato, Hiroyoshi Nishikawa, Masaaki Ito, Takayuki Yoshino
Organizer
ASCO2020
Related Report
Int'l Joint Research
-
-
-