Novel immunoediting mechanisms via somatic mutations
Project/Area Number |
19K22574
|
Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 50:Oncology and related fields
|
Research Institution | Chiba Cancer Center (Research Institute) |
Principal Investigator |
Togashi Yosuke 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, 部長代理 (80758326)
|
Project Period (FY) |
2019-06-28 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
|
Keywords | がん免疫編集 / 腫瘍免疫 / ネオ抗原 |
Outline of Research at the Start |
発がん過程で、がんは抗腫瘍免疫応答から逃れるため免疫制御機構を巧みに利用している(「がん免疫編集」)。体細胞変異数が多いと異物として認識される抗原(ネオ抗原)も多いため免疫原性が高くがん免疫療法の効果が高いとされている。しかし予備検討で体細胞変異数が極端に多い場合には免疫応答が抑制され、特定の免疫抑制シグナルの遺伝子セットの発現が高いことを見出した。そこで本研究課題では体細胞変異数が極端に多いが免疫応答が抑制されている症例でのT細胞の実際のネオ抗原への反応や、原因シグナルやゲノム異常を明らかにし、従来の「がん免疫編集」に加えた新たな免疫編集機構の提唱を目指す。
|
Outline of Final Research Achievements |
Cancer cells with high tumor mutation burden (TMB) can have a more malignant phenotype, but strong antitumor immunity can be also induced by high TMB. Here, we have found that a fraction of patients has non-inflamed tumor microenvironment despite high TMB due to some signaling pathways related to the malignant phenotype and we could validate several pathways using mouse models. From these findings, novel immunoediting mechanisms via somatic mutations is proposed, and we should consider not only just simple TMB but also the quality.
|
Academic Significance and Societal Importance of the Research Achievements |
従来の「がん免疫編集」に加えて、がんが悪性度に関わるようなシグナルを巧みに利用して免疫系から逃れているという新たながん免疫編集を明らかにした。そのような悪性度に関わるシグナルもいくつか同定し、それらはがん免疫療法の治療標的になる可能性があり、今後のバイオマーカーや併用療法としての新たな治療開発に繋がるデータである。
|
Report
(3 results)
Research Products
(62 results)
-
-
-
-
-
[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
-
-
-
[Journal Article] Clinical and immune profiling for cancer of unknown primary site.2019
Author(s)
Haratani K, Hayashi H, Takahama T, Nakamura Y, Tomida S, Yoshida T, Chiba Y, Sawada T, Sakai K, Fujita Y, Togashi Y, Tanizaki J, Kawakami H, Ito A, Nishio K, Nakagawa K
-
Journal Title
Journal for immunotherapy of cancer
Volume: 7
Issue: 1
Pages: 251-251
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[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 lymphoma.2021
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 Cancer2021
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
Int'l Joint Research
-
-
-
-
-
-
-
-
[Presentation] Translational research of voltage-A1: Efficacy predictors of preoperative chemoradiotherapy and subsequent nivolumab monotherapy in patients with microsatellite-stable locally advanced rectal cancer2020
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
-
-
-
-
-
-
-
-
[Presentation] Multiple modalities of single cell analyses to evaluate the tumor microenvironment in clinical specimens2019
Author(s)
Yukie Kashima, Shota Fukuoka, Yosuke Togashi, Takahiro Kamada, Ayako Suzuki, Yoshiaki Nakamura, Kohei Shitara, Akihiro Ohashi, Taku Yoshida, Naofumi Taoka, Tatsuya Kawase, Teiji Wada, Kocihiro Inaki, Masataka Chihara, Yutaka Suzuki, Katsuya Tsuchihara, Susumu S Kobayashi, Hiroyoshi Nishikawa and Toshihiko Doi
Organizer
EORTC-AACR
Related Report
Int'l Joint Research
-
-
[Presentation] Regorafenib plus nivolumab in patients with advanced gastric (GC) or colorectal cancer (CRC): an open-label, dose-finding, and dose-expansion phase 1b trial (REGONIVO, EPOC1603)2019
Author(s)
Shota Fukuoka, Hiroki Hara, Naoki Takahashi, Takashi Kojima, Akihito Kawazoe, Masako Asayama, Takako Yoshii, Daisuke Kotani, Hitomi Tamura, Yuichi Mikamoto, Ayako Sugama, Masashi Wakabayashi, Shogo Nomura, Akihiro Sato, Yosuke Togashi, Hiroyoshi Nishikawa, Kohei Shitara
Organizer
第17回日本臨床腫瘍学会学術集会
Related Report
-
-
[Presentation] The PD-1 expression balance between effector and regulatory T cell predicts the clinical efficacy of PD-1 blockade therapies2019
Author(s)
Yosuke Togashi, Takahiro Kamada, Eri Sugiyama, Shota Fukuoka, Akihito Kawazoe, Hibiki Udagawa, Keisuke Kirita, Koichi Goto, Masahiro Tsuboi, Toshihiko Doi, Kohei Shitara, Hiroyoshi Nishikawa
Organizer
第17回日本臨床腫瘍学会学術集会
Related Report
-
[Presentation] Novel concept of EGFR-signal contribution to unique immunological status of the tumor microenvironment in EGFR-mutated NSCLC2019
Author(s)
Eri Sugiyama, Yosuke Togashi, Yoshiko Takeuchi, Sayoko Shinya, Yasuko Tada, Keisuke Kataoka, Kenta Tane, Genichiro Ishii, Koichi Goto, Yasushi Shintani, Meinoshin Okumura, Masahiro Tsuboi, Hiroyoshi Nishikawa
Organizer
第17回日本臨床腫瘍学会学術集会
Related Report
-
[Presentation] Combination of triplet soluble immune-checkpoint factors as a complementary biomarker for the efficacy of nivolumab (nivo) in advanced non-small cell lung cancer (NSCLC) patients (pts)2019
Author(s)
Hidetoshi Hayashi, Kenji Chamoto, Yosuke Togashi, Kazuya Fukuoka, Ryusuke Hatae, Megumi Goto, Yasutaka Chiba, Junko Tanizaki,1,6 Koji Haratani, Takayuki Takahama, Kaoru Tanaka, Masayuki Takeda, Kazuko Sakai, Keiko Higuchi, Hitoshi Uga, Kazuto Nishio, Kazuhiko Nakagawa, Tasuku Honjo
Organizer
第17回日本臨床腫瘍学会学術集会
Related Report
-
[Presentation] Efficacy of Radiotherapy to Primary Tumor After Nivolumab Treatment in Patients with Advanced Gastric Cancer2019
Author(s)
Akinori Sasaki, Yoshiaki Nakamura, Hirofumi Kuno, Yosuke Togashi, Hidehiro Hojo, Kenji Takashima, Tomohiro Kadota, Saori Mishima, Daisuke Kotani, Akihito Kawazoe, Yasutoshi Kuboki, Hiroya Taniguchi,Takayuki Yoshino, Tatsushi Kobayashi, Hiroyoshi Nishikawa, Naoki Nakamura, Tomonori Yano, Kohei Shitara
Organizer
第17回日本臨床腫瘍学会学術集会
Related Report
-
[Presentation] 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 Carcinoma2019
Author(s)
Hideaki Bando, Daisuke Kotani, Takahiro Tsushima, Hiroki Hara, Shigenori Kadowaki, Ken Kato, Keisho Chin, Kensei Yamaguchi, Shun-ichiro Kageyama, Hidehiro Hojo, Shogo Nomura, Miki Fukutani, Yosuke Togashi, Nozomu Fuse, Hiroyoshi Nishikawa, and Takashi Kojima
Organizer
ASCO Annual Meeting
Related Report
Int'l Joint Research
-
[Presentation] Regorafenib plus nivolumab in patients with advanced gastric (GC) or colorectal cancer (CRC): an open-label, dose-finding, and dose-expansion phase 1b trial (REGONIVO, EPOC1603)2019
Author(s)
Shota Fukuoka, Hiroki Hara, Naoki Takahashi, Takashi Kojima, Akihito Kawazoe, Masako Asayama, Takako Yoshii, Daisuke Kotani, Hitomi Tamura, Yuichi Mikamoto, Ayako Sugama, Masashi Wakabayashi, Shogo Nomura, Akihiro Sato, Yosuke Togashi, Hiroyoshi Nishikawa, Kohei Shitara
Organizer
ASCO Annual Meeting
Related Report
Int'l Joint Research
-
[Presentation] VOLTAGE: Investigator-initiated Clinical Trial of Nivolumab Monotherapy and Subsequent Radical Surgery Following Preoperative Chemoradiotherapy in Patients with Microsatellite Stable Locally Advanced Rectal Cancer2019
Author(s)
Takayuki Yoshino, Hideaki Bando, Yuichiro Tsukada, Koji Inamori, Satoshi Yuki, Yoshito Komatsu, Shigenori Homma, Mamoru Uemura, Takeshi Kato, Daisuke Kotani, Shota Fukuoka, Yosuke Togashi, Akihiro Sato, Hiroyoshi Nishikawa, Masaaki Ito
Organizer
ASCO Annual Meeting
Related Report
Int'l Joint Research
-
[Presentation] An Open Label Phase I Study to Evaluate the Safety and Efficacy of OBP-301 With Pembrolizumab in Patients With Advanced Solid Tumors (EPOC1505)2019
Author(s)
Takashi Kojima, Toshiyoshi Fujiwara, Yasuhiro Shirakawa, Keisuke Hori, Hiromi Ono, Masako Nakamoto, Hiromi Hasegawa, Nami Hirano, Masashi Wakabayashi, Shogo Nomura, Yosuke Togashi, Hiroyoshi Nishikawa, Akihiro Sato, Atsushi Ohtsu, Toshihiko Doi
Organizer
AACR Annual Meeting
Related Report
Int'l Joint Research
-
-
-
-