Association of immune responses with racial differences of cancer development

2019 Fiscal Year Annual Research Report

• Project/Area Number: 17H06162
• Research Institution: Nagoya University
• Principal Investigator: 西川 博嘉 名古屋大学, 医学系研究科, 教授 (10444431)
• 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)
• Project Period (FY): 2017-05-31 – 2022-03-31
• Keywords: 腫瘍免疫 / 発がん / がん免疫療法

Outline of Annual Research Achievements

本研究は、ドライバー遺伝子変異と発がんの人種差という腫瘍学および免疫学の長年の大きな課題に対してチャレンジすることで、免疫監視が作動しているHLAタイプでのT細胞応答を再現し、抗腫瘍免疫応答の本態を解明することを目的として実施した。すでに遺伝子変異が、がん局所の免疫応答に与える影響について解析を進め、ケモカイン環境の変化および代謝環境の変化を通じて免疫細胞浸潤に影響を与えることで、がん局所に強力な免疫抑制ネットワークを構築していることを明らかにした。さらにこれらのデータに基づき、現在臨床展開が進むがん免疫療法において、ドライバー遺伝子変異に対する阻害剤と免疫療法の併用の可能性を示し、発がんに関わる免疫応答に基づいたがん免疫療法の新たな併用療法の指針となったる。
また、がん細胞で見られる遺伝子変異に対する免疫応答の解析（免疫監視側）からCD8+T細胞上のPD-1発現が TCRシグナル強度に依存していることを明らかにした。つまり、PD-1発現CD8+T細胞は、TCRに高親和性の抗原 (がん退縮に関連する遺伝子異常に由来するネオ抗原) 刺激を受けたと考えられることを明らかにし、抗腫瘍効果の本態に関わるエフェクター細胞である可能性を示した。一方、制御性T細胞上にも同様にPD-1発現がみられ、TCRおよび共刺激シグナルを減弱させることにより、疲弊状態を引き起こしていることを世界に先駆けて解明した。以上より、ネオ抗原から強いTCRシグナルを受けたCD8+T細胞ががん局所に多数存在し、免疫チェックポイント阻害剤によりそれらのCD8+T細胞の再活性化が優位であることが抗腫瘍活性につながっていることを明らかにし、CD8+T細胞上のPD-1発現と制御性T細胞上のPD-1発現レベルの差がPD－１阻害剤への反応性を規定する重要な因子であるというがん免疫療法の効果予測バイオマーカーに展開した。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

本研究では、３つを研究目的について以下の様に計画以上の進展が見られている。
1) すでに15万人からなる日本人を対象とした肺腺癌および大腸癌に対する全ゲノム関連解析を実施し、HLA領域に複数の感受性遺伝子座を同定するに至っている。
2) 1)で得られた遺伝子解析情報をもとに、免疫監視が作動している、もしくは作動していないHLAで、抗原提示されることが予測される遺伝子変異由来の異常タンパク質およびペプチドを作成した。これらを用いて、現在特異的CD8+T細胞を誘導し、分子発現、細胞機能の検討を進め、すでに遺伝子変異に対する免疫応答の解析から、CD8+T細胞上のPD-1発現がTCRシグナル強度に依存していることを解明し、抗腫瘍効果の本態に関わるエフェクター細胞である可能性を示した。さらに、ドライバー遺伝子変異自身が、がん局所の免疫応答に与える影響について解析を進め、がん局所に強力な免疫抑制ネットワークを構築しているメカニズムを明らかにし、予想を超える成果が得られていると考えている。
3) ヒトHLAのトランスジェニックマウスを作成するとともにヒト検体を用いて、T細胞応答を検討する点についても細胞株での検討は、EGFRや他のドライバー遺伝子変異などについても細胞株を作成して検討を進め、ドライバー遺伝子変異自身が免疫抑制に直接関わっていることを解明した。また、発がんモデルマウスも作成が完了し、野生型マウスで発がんが認められた。一方、発がんリスクにかかわるHLA class Iアリルをトランスジェニックしたマウスについても作成が終了し、十分な繁殖が得られ、これらのマウスを用いた検討を現在順調に進めている。

Strategy for Future Research Activity

研究を進める上で生じた問題点については、現在、全て解決でき、計画以上の研究進展が見えらているこことから、当初の研究計画調書から変更なく研究を進める。また研究代表者および研究分担者についても、現在のところ退職や異動の予定はなく、当初の研究体制を維持し、今後の研究を進めていく。

Research Products

• [Int'l Joint Research] Memorial Sloan Kettering Cancer Center(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: Memorial Sloan Kettering Cancer Center
• [Journal Article] Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR-mutated non-small cell lung cancer (2020)
  • Author(s): Sugiyama E, Togashi Y, Takeuchi Y, Shinya S, Tada Y, Kataoka K, Tane K, Sato E, Ishii G, Goto K, Shintani Y, Okumura M, Tsuboi M, Nishikawa H
  • Journal Title: Science Immunology Volume: 5 Pages: 3937
  • DOI: 10.1126/sciimmunol.aav3937
  • Peer Reviewed
• [Journal Article] Tyrosine kinase inhibitor imatinib augments tumor immunity by depleting effector regulatory T cells (2020)
  • Author(s): Tanaka A, Nishikawa H, Noguchi S, Sugiyama D, Morikawa H, Takeuchi Y, Ha D, Shigeta N, Kitawaki T, Maeda Y, Saito T, Shinohara Y, Kameoka Y, Iwaisako K, Monma F, Ohishi K, Karbach J, Jager E, Sawada K, Katayama N, Takahashi N, Sakaguchi S
  • Journal Title: J Exp Med Volume: 217 Pages: -
  • DOI: 10.1084/jem.20191009
  • Peer Reviewed
• [Journal Article] Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women (2020)
  • Author(s): Wong JYY, Zhang H, Hsiung CA, Shiraishi K,Kohno T, Shen H, Chanock SJ, Rothman N, Lan Q
  • Journal Title: Genomics Volume: 112 Pages: 1223-1232
  • DOI: 10.1016/j.ygeno.2019.07.008
  • Peer Reviewed
• [Journal Article] Selective inhibition of low-affinity memory CD8+ T cells by corticosteroids (2019)
  • Author(s): Tokunaga A, Sugiyama D, Maeda Y, Warner AB, Panageas KS, Ito S, Togashi Y, Sakai C, Wolchok JD, Nishikawa H
  • Journal Title: J Exp Med Volume: 216 Pages: 2701-2713
  • DOI: 10.1084/jem.20190738
  • Peer Reviewed
• [Journal Article] The potential application of PD-1 blockade therapy for early-stage biliary tract cancer (2019)
  • 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 Pages: 273-281
  • DOI: 10.1093/intimm/dxz080
  • Peer Reviewed
• [Journal Article] PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer (2019)
  • Author(s): Kamada T, Togashi Y, Tay C, Ha D, Sasaki A, Nakamura Y, Sato E, Fukuoka S, Tada Y, Tanaka A, Morikawa H, Kawazoe A, Kinoshita T, Shitara K, Sakaguchi S, Nishikawa H
  • Journal Title: Proc Natl Acad Sci USA Volume: 116 Pages: 9999-10008
  • DOI: 10.1073/pnas.1822001116
  • Peer Reviewed
• [Journal Article] Immune suppression by PD-L2 against spontaneous and treatment-related antitumor immunity (2019)
  • Author(s): Tanegashima T, Togashi Y, Azuma K, Kawahara A, Ideguchi K, Sugiyama D, Kinoshita F, Akiba J, Kashiwagi E, Takeuchi A, Irie T, Tatsugami K, Hoshino T, Eto M. Nishikawa H
  • Journal Title: Clin Cancer Res Volume: 25 Pages: 4808-4819
  • DOI: 10.1158/1078-0432.CCR-18-3991
  • Peer Reviewed
• [Journal Article] Regulatory T cells in cancer immunosuppression - Implications for anticancer therapy (2019)
  • Author(s): Togashi Y, Shitara K, Nishikawa H
  • Journal Title: Nat Rev Clin Oncol Volume: 16 Pages: 356-371
  • DOI: 10.1038/s41571-019-0175-7
  • Peer Reviewed
• [Journal Article] Regulatory T (Treg) cells in cancer: can Treg cells be a new therapeutic target? (2019)
  • Author(s): Ohue Y, Nishikawa H
  • Journal Title: Cancer Sci Volume: 110 Pages: 2080-2089
  • DOI: 10.1111/cas.14069
  • Peer Reviewed
• [Journal Article] Meddling with meddlers: curbing regulatory T cells and augmenting antitumor immunity (2019)
  • Author(s): Kochin V, Nishikawa H
  • Journal Title: Nagoya J Med Sci Volume: 81 Pages: 1-18
  • DOI: 10.18999/nagjms.81
  • Peer Reviewed
• [Journal Article] A Phase I Study of the Anti-CC Chemokine Receptor 4 Antibody, Mogamulizumab, in Combination with Nivolumab in Patients with Advanced or Metastatic Solid Tumors (2019)
  • Author(s): Doi T, Muro K, Ishii H, Kato T, Tsushima T, Takenoyama M, Oizumi S, Gemmoto K, Suna H, Enokitani K, Kawakami T, Nishikawa H, Yamamoto N
  • Journal Title: Clin Cancer Res Volume: 25 Pages: 6614-6622
  • DOI: 10.1158/1078-0432.CCR-19-1090
  • Peer Reviewed
• [Journal Article] Differential control of human Treg and effector T cells in tumor immunity by Fc-engineered anti-CTLA-4 antibody (2019)
  • Author(s): Ha D, Tanaka A, Kibayashi T, Tanemura A, Sugiyama D, Wing JB, Lim EL, Teng KWW, Adeegbe D, Newell EW, Katayama I, Nishikawa H, Sakaguchi S
  • Journal Title: Proc Natl Acad Sci USA Volume: 116 Pages: 609-618
  • DOI: 10.1073/pnas.1812186116
  • Peer Reviewed
• [Journal Article] Model-based cell clustering and population tracking for time-series flow cytometry data (2019)
  • Author(s): Minoura K, Abe K, Maeda Y, Nishikawa H, Shimamura T
  • Journal Title: BMC Bioinformatics Volume: 20 Pages: 633
  • DOI: 10.1186/s12859-019-3294-3
  • Peer Reviewed
• [Journal Article] Analysis of the Tumor Reactivity of Tumor-Infiltrating Lymphocytes in a Metastatic Melanoma Lesion that Lost Major Histocompatibility Complex Class I Expression after Anti-PD-1 Therapy (2019)
  • Author(s): Inozume T, Yaguchi T, Ariyasu R, Togashi Y, Ohnuma T, Honobe A, Nishikawa H, Kawakami Y, Kawamura T
  • Journal Title: J Invest Dermatol Volume: 139 Pages: 1490-1496
  • DOI: 10.1016/j.jid.2019.01.007
  • Peer Reviewed
• [Journal Article] Clinicopathological features of 22C3 PD-L1 expression with mismatch repair, Epstein-Barr virus status, and cancer genome alterations in metastatic gastric cancer (2019)
  • Author(s): Kawazoe A, Shitara K, Kuboki Y, Bando H, Kojima T, Yoshino T, Ohtsu A, Ochiai A, Togashi Y, Nishikawa H, Doi T, Kuwata T
  • Journal Title: Gastric Cancer Volume: 22 Pages: 69-76
  • DOI: 10.1007/s10120-018-0843-9
  • Peer Reviewed
• [Journal Article] A phase I study of ontuxizumab, a humanized monoclonal antibody targeting endosialin, in Japanese patients with solid tumors (2019)
  • Author(s): Doi T, Aramaki T, Yasui H, Muro K, Ikeda M, Okusaka T, Inaba Y, Nakai K, Ikezawa H, Nakajima R
  • Journal Title: Invest New Drugs Volume: 37 Pages: 1061-1074
  • DOI: 10.1007/s10637-018-0713-7
  • Peer Reviewed
• [Journal Article] Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced, PD-L1-positive papillary or follicular thyroid cancer (2019)
  • Author(s): Mehnert JM, Varga A, Brose MS, Aggarwal RR, Lin CC, Prawira A, de Braud F, Tamura K, Doi T, Piha-Paul SA, Gilbert J, Saraf S, Thanigaimani P, Cheng JD, Keam B
  • Journal Title: BMC Cancer Volume: 19 Pages: 196
  • DOI: 10.1186/s12885-019-5380-3
  • Peer Reviewed
• [Journal Article] First-in-Human Phase I Study of an Oral HSP90 Inhibitor, TAS-116, in Patients with Advanced Solid Tumors (2019)
  • Author(s): Shimomura A, Yamamoto N, Kondo S, Fujiwara Y, Suzuki S, Yanagitani N, Horiike A, Kitazono S, Ohyanagi F, Doi T, Kuboki Y, Kawazoe A, Shitara K, Ohno I, Banerji U, Sundar R, Ohkubo S, Calleja EM, Nishio M
  • Journal Title: Mol Cancer Ther Volume: 18 Pages: 531-540
  • DOI: 10.1158/1535-7163.MCT-18-0831
  • Peer Reviewed
• [Journal Article] Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study (2019)
  • Author(s): Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T, Lee C, Sugihara M, Shahidi J, Yver A, Modi S
  • Journal Title: Lancet Oncol Volume: 20 Pages: 816-826
  • DOI: 10.1016/S1470-2045(19)30097-X
  • Peer Reviewed
• [Journal Article] Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study (2019)
  • Author(s): Shitara K, Iwata H, Takahashi S, Tamura K, Park H, Modi S, Tsurutani J, Kadowaki S, Yamaguchi K, Iwasa S, Saito K, Fujisaki Y, Sugihara M, Shahidi J, Doi T
  • Journal Title: Lancet Oncol Volume: 20 Pages: 827-836
  • DOI: 10.1016/S1470-2045(19)30088-9
  • Peer Reviewed
• [Journal Article] First-in-human phase 1 study of novel dUTPase inhibitor TAS-114 in combination with S-1 in Japanese patients with advanced solid tumors (2019)
  • Author(s): Doi T, Yoh K, Shitara K, Takahashi H, Ueno M, Kobayashi S, Morimoto M, Okusaka T, Ueno H, Morizane C, Okano N, Nagashima F, Furuse J
  • Journal Title: Invest New Drugs Volume: 37 Pages: 507-518
  • DOI: 10.1007/s10637-018-0697-3
  • Peer Reviewed
• [Journal Article] Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study (2019)
  • Author(s): Bang YJ, Kang YK, Catenacci DV, Muro K, Fuchs CS, Geva R, Hara H, Golan T, Garrido M, Jalal SI, Borg C, Doi T, Yoon HH, Savage MJ, Wang J, Dalal RP, Shah S, Wainberg ZA, Chung HC
  • Journal Title: Gastric Cancer Volume: 22 Pages: 828-837
  • DOI: 10.1007/s10120-018-00909-5
  • Peer Reviewed
• [Journal Article] Predictive factors for hyperprogressive disease during nivolumab as anti-PD1 treatment in patients with advanced gastric cancer (2019)
  • Author(s): Sasaki A, Nakamura Y, Mishima S, Kawazoe A, Kuboki Y, Bando H, Kojima T, Doi T, Ohtsu A, Yoshino T, Kuwata T, Akimoto T, Shitara K
  • Journal Title: Gastric Cancer Volume: 22 Pages: 793-802
  • DOI: 10.1007/s10120-018-00922-8
  • Peer Reviewed
• [Journal Article] Phase 1 trial of avelumab (anti-PD-L1) in Japanese patients with advanced solid tumors, including dose expansion in patients with gastric or gastroesophageal junction cancer: the JAVELIN Solid Tumor JPN trial (2019)
  • Author(s): Doi T, Iwasa S, Muro K, Satoh T, Hironaka S, Esaki T, Nishina T, Hara H, Machida N, Komatsu Y, Shimada Y, Otsu S, Shimizu S, Watanabe M
  • Journal Title: Gastric Cancer Volume: 22 Pages: 817-827
  • DOI: 10.1007/s10120-018-0903-1
  • Peer Reviewed
• [Journal Article] Clinicopathological and molecular features of responders to nivolumab for patients with advanced gastric cancer (2019)
  • Author(s): Mishima S, Kawazoe A, Nakamura Y, Sasaki A, Kotani D, Kuboki Y, Bando H, Kojima T, Doi T, Ohtsu A, Yoshino T, Kuwata T, Tsuji A, Shitara K
  • Journal Title: J Immunother Cancer Volume: 7 Pages: 24
  • DOI: 10.1186/s40425-019-0514-3
  • Peer Reviewed
• [Journal Article] T-Cell-Inflamed Gene-Expression Profile, Programmed Death Ligand 1 Expression, and Tumor Mutational Burden Predict Efficacy in Patients Treated With Pembrolizumab Across 20 Cancers: KEYNOTE-028 (2019)
  • Author(s): Ott PA, Bang YJ, Piha-Paul SA, Razak ARA, Bennouna J, Soria JC, Rugo HS, Cohen RB, O'Neil BH, Mehnert JM, Lopez J, Doi T, van Brummelen EMJ, Cristescu R, Yang P, Emancipator K, Stein K, Ayers M, Joe AK, Lunceford JK
  • Journal Title: J Clin Oncol Volume: 37 Pages: 318-327
  • DOI: 10.1200/JCO.2018.78.2276
  • Peer Reviewed
• [Journal Article] Phase I Study of the Focal Adhesion Kinase Inhibitor BI 853520 in Japanese and Taiwanese Patients with Advanced or Metastatic Solid Tumors (2019)
  • Author(s): Doi T, Yang JC, Shitara K, Naito Y, Cheng AL, Sarashina A, Pronk LC, Takeuchi Y, Lin CC
  • Journal Title: Targeted Oncol Volume: 14 Pages: 57-65
  • DOI: 10.1007/s11523-019-00620-0
  • Peer Reviewed
• [Journal Article] Phase I study of ipatasertib as a single agent and in combination with abiraterone plus prednisolone in Japanese patients with advanced solid tumors (2019)
  • Author(s): Doi T, Fujiwara Y, Matsubara N, Tomomatsu J, Iwasa S, Tanaka A, Endo-Tsukude C, Nakagawa S, Takahashi S
  • Journal Title: Cancer Chemother Pharmacol Volume: 84 Pages: 393-404
  • DOI: 10.1007/s00280-019-03882-7
  • Peer Reviewed
• [Journal Article] A phase 1 study of oral ASP5878, a selective small-molecule inhibitor of fibroblast growth factor receptors 1-4, as a single dose and multiple doses in patients with solid malignancies (2019)
  • Author(s): Yamamoto N, Ryoo BY, Keam B, Kudo M, Lin CC, Kunieda F, Ball HA, Moran D, Komatsu K, Takeda K, Fukuda M, Furuse J, Morita S, Doi T
  • Journal Title: Invest New Drugs Volume: 38 Pages: 445-456
  • DOI: 10.1007/s10637-019-00780-w
  • Peer Reviewed
• [Journal Article] Phase I dose-escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors (2019)
  • Author(s): Esaki T, Hirai F, Makiyama A, Seto T, Bando H, Naito Y, Yoh K, Ishihara K, Kakizume T, Natsume K, Myers A, Doi T
  • Journal Title: Cancer Sci Volume: 110 Pages: 1340-1351
  • DOI: 10.1111/cas.13956
  • Peer Reviewed
• [Journal Article] KEYNOTE-590: Phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer (2019)
  • Author(s): Kato K, Shah MA, Enzinger P, Bennouna J, Shen L, Adenis A, Sun JM, Cho BC, Ozguroglu M, Kojima T, Kostorov V, Hierro C, Zhu Y, McLean LA, Shah S, Doi T
  • Journal Title: Future Oncol Volume: 15 Pages: 1057-1066
  • DOI: 10.2217/fon-2018-0609
  • Peer Reviewed
• [Journal Article] Characterization and phase I study of CLR457, an orally bioavailable pan-class I PI3-kinase inhibitor (2019)
  • Author(s): Harding JJ, Bauer TM, Tan DSW, Bedard PL, Rodon J, Doi T, Schnell C, Iyer V, Baffert F, Radhakrishnan R, Fabre C, Juric D
  • Journal Title: Invest New Drugs Volume: 37 Pages: 271-281
  • DOI: 10.1007/s10637-018-0627-4
  • Peer Reviewed
• [Journal Article] Body Mass Index (BMI), BMI Change, and Overall Survival in Patients With SCLC and NSCLC: A Pooled Analysis of the International Lung Cancer Consortium (2019)
  • Author(s): Shepshelovich D, Xu W,Kohno T, Harris CC, Wenzlaff AS, Fernandez-Tardon G, Ye Y, Taylor F, Wilkens LR, Davies M, Liu Y, Barnett MJ, Goodman GE, Morgenstern H, Holleczek B, Brown MC, Liu G, Hung RJ
  • Journal Title: J Thorac Oncol Volume: 14 Pages: 1594-1607
  • DOI: 10.1016/j.jtho.2019.05.031
  • Peer Reviewed
• [Presentation] Updated results from a phase Ib trial of regorafenib plus nivolumab in patients with advanced colorectal or gastric cancer (2020)
  • Author(s): Shitara K, Hara H, Takahashi N, Kojima T, Kawazoe A, Asayama M, Yoshii T, Kotani D, Tamura H, Mikamoto Y, Hirano N, Wakabayashi M, Nomura S, Sato A, Nishikawa H, Fukuoka S
  • Organizer: 2020 Gastrointestinal Cancers Symposium
  • Int'l Joint Research
• [Presentation] Multicenter phase I/II trial of BBI608 and pembrolizumab in patients with metastatic colorectal cancer (2020)
  • Author(s): Hara H, Kawazoe A, Kuboki Y, Komatsu Y, Nishina T, Shinozaki E, Yuki S, Takahashi K, Mikamoto Y, Hirano N, Nomura S, Togashi Y, Nishikawa H, Sato A, Ohtsu A, Yoshino T
  • Organizer: 2020 Gastrointestinal Cancers Symposium
  • Int'l Joint Research
• [Presentation] VOLTAGE-B Study: Nivolumab monotherapy and subsequent curative surgery following preoperative chemoradiotherapy in patients with locally recurrent rectal cancer (LRRC) without previous radiotherapy (2020)
  • Author(s): Kato T, Bando H, Tsukada Y, Inamori K, Uemura M, Yuki S, Komatsu Y, Homma S, Kotani D, Fukuoka S, Sasaki T, Nishizawa Y, Nakamura N, Wakabayashi M, Kojima M, Togashi Y, Sato A, Nishikawa H, Yoshino T, Ito M
  • Organizer: 2020 Gastrointestinal Cancers Symposium
  • Int'l Joint Research
• [Presentation] がん細胞および免疫応答解析に基づくがん免疫療法効果予測診断法の確立 (2020)
  • Author(s): 西川博嘉
  • Organizer: 令和元年度HTLV-1関連疾患研究領域研究班合同発表会
  • Invited
• [Presentation] Tumor microenvironment influences to guide immuno-oncology utilization (2019)
  • Author(s): Nishikawa H
  • Organizer: The 6th Immuno-Oncology Academy
  • Int'l Joint Research / Invited
• [Presentation] Regulatory T Cells in The Tumor Microenvironment and Cancer Progression: What's New in Therapeutic Targeting Strategies? (2019)
  • Author(s): Nishikawa H
  • Organizer: 2019 ASCO ANNUAL MEETING
  • Int'l Joint Research / Invited
• [Presentation] Regulatory T cells in the tumour microenvironment (2019)
  • Author(s): Nishikawa H
  • Organizer: HHMT14th International Forum on Ovarian Cancer
  • Int'l Joint Research / Invited
• [Presentation] がん微小環境の免疫抑制機構とがん免疫療法 (2019)
  • Author(s): 西川博嘉
  • Organizer: 第34回日本臨床リウマチ学会
  • Invited
• [Presentation] がん局所の免疫抑制ネットワークからみたがん免疫療法 (2019)
  • Author(s): 西川博嘉
  • Organizer: 日本放射線腫瘍学会第32会学術大会
  • Invited
• [Presentation] Immune Suppressive Mechanisms in Tumor Microenvironment as a Target of Novel Cancer Immunotherapy (2019)
  • Author(s): Nishikawa H
  • Organizer: 第50回記念 高松宮妃癌研究財団国際シンポジウム
  • Invited
• [Presentation] T cell suppression in the tumor microenvironment (2019)
  • Author(s): Nishikawa H
  • Organizer: The 10th annual meeting of ACTO
  • Invited
• [Presentation] がん微小環境における免疫抑制ネットワーク (2019)
  • Author(s): 西川博嘉
  • Organizer: 第57回日本癌治療学会学術集会
  • Invited
• [Presentation] がん微小環境の免疫抑制ネットワークの理解とがん免疫療法への展開 (2019)
  • Author(s): 西川博嘉
  • Organizer: 第62回日本口腔科学会中部地方部会学術集会
  • Invited
• [Presentation] 腫瘍微小環境での免疫抑制ネットワーク (2019)
  • Author(s): 西川博嘉
  • Organizer: 第78回日本癌学会学術総会
  • Invited
• [Presentation] がん微小環境の免疫抑制ネットワークとがん免疫療法 (2019)
  • Author(s): 西川博嘉
  • Organizer: 第31回高遠・分子細胞生物学シンポジウム
  • Invited
• [Presentation] 臨床応用が進むがん免疫療法の基礎 (2019)
  • Author(s): 西川博嘉
  • Organizer: 第84回日本インターフェロン・サイトカイン学会学術集会
  • Invited
• [Presentation] 血液悪性疾患治療における免疫反応の重要性（The importance of immune responses in the treatment of hematologic malignancies） (2019)
  • Author(s): 西川博嘉
  • Organizer: 第17回日本臨床腫瘍学会学術集会
  • Invited
• [Presentation] がん免疫療法、過去、現在、そして未来, 口頭, 市民公開講座 (2019)
  • Author(s): 西川博嘉
  • Organizer: 第118回日本皮膚科学会総会
  • Invited
• [Presentation] がん免疫療法の臨床応用によってわかったことと今後の課題 (2019)
  • Author(s): 西川博嘉
  • Organizer: 第105回日本消化器病学会総会
  • Invited
• [Presentation] 新しい解析技術によるがん免疫研究 (2019)
  • Author(s): 西川博嘉
  • Organizer: 第63回日本リウマチ学会総会・学術集会
  • Invited
• [Presentation] Immune suppressive network within the tumor microenvironment (2019)
  • Author(s): Nishikawa H
  • Organizer: Nagoya Immunology Network in NCU The first international symposium
  • Invited
• [Presentation] A novel regulatory T cell-targeted immunotherapy via meddling the crucial signal by HSP90 inhibitors (2019)
  • Author(s): 柘植彩花、冨樫庸介、西川博嘉
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] ステロイドによる脂肪酸代謝阻害を介したメモリーCD8陽性T細胞の選択的抑制 (2019)
  • Author(s): 前田優香、徳永昌浩、杉山大介、ワーナー アリソン、ウォルチョク ジェド、西川博嘉
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] 腫瘍に発現するPD-L2の免疫抑制機能について (2019)
  • Author(s): 種子島時祥、冨樫庸介、東公一、江藤正俊、西川博嘉
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] A Novel Regulatory T Cell-Targeted Immunotherapy by targeting their Crucial Signal by HSP90 Inhibitors (2019)
  • Author(s): Tsuge A, Togashi Y, Shitara K, Nishikawa H
  • Organizer: SITC 2019
  • Int'l Joint Research
• [Presentation] Clinical utility of precision immunoprofiling and monitoring of the tumor microenvironment using flow cytometry and CyTOF in patients with advanced NSCLC treated with atezolizumab: results from a phase II study for biomarker analysis (EPOC1702) (2019)
  • Author(s): Kirita K, Sugiyama E, Togashi Y, Udagawa H, Irie T, Iida S, Nakamoto M, Nomura S, Ikeda T, Zenke Y, Matsumoto S, Yoh K, Niho S, Sato A, Nishikawa H,Goto H
  • Organizer: ESMO Congress 2019
  • Int'l Joint Research
• [Presentation] 転移性腎細胞癌に対するニボルマブ治療が奏功し原発巣を摘除し得た1例 (2019)
  • Author(s): 種子島時祥、塚原茂大、池之上俊、大坪智志、長谷川周二、西川博嘉、江藤正俊
  • Organizer: 第23回日本がん免疫学会総会
• [Presentation] Novel concept of EGFR-signal contribution to unique immunological status in EGFR-mutated NSCLC (2019)
  • Author(s): Sugiyama E, Togashi Y, Takeuchi Y, Shinya S, Tada Y, Kataoka K, Tane K, Ishii G, Goto K, Shintani Y, Okumura M, Tsuboi M, Nishikawa H
  • Organizer: 第17回日本臨床腫瘍学会学術集会
• [Presentation] Clinical utility of precision immunoprofiling and monitoring of the tumor microenvironment using flow cytometry and CyTOF in patients with advanced NSCLC treated with atezolizumab: results from a phase II study for biomarker analysis (2019)
  • Author(s): Kirita K, Sugiyama E, Togashi Y, Udagawa H, Irie T, Iida S, Nakamoto M, Nomura S, Ikeda T, Zenke Y, Matsumoto S, Yoh K, Niho S, Sato A, Nishikawa H, Goto K
  • Organizer: 第17回日本臨床腫瘍学会学術集会
• [Presentation] Primary tumor resection after nivolumab treatment for metastatic renal cell carcinoma: A case report (2019)
  • Author(s): Tanegashima T, Tsukahara S, Ikenoue T, Otsubo S, Hasegawa S, Nishikawa H, Eto M
  • Organizer: 第17回日本臨床腫瘍学会学術集会
• [Presentation] 腫瘍に発現するPD-L2の免疫抑制機能について (2019)
  • Author(s): 種子島時祥、江藤正俊、西川博嘉
  • Organizer: 第50回腎癌研究会
• [Presentation] 免疫抑制機構に着目したがん免疫療法 (2019)
  • Author(s): 西川博嘉
  • Organizer: 第30回日本医学会総会2019中部
• [Presentation] 基礎研究からみたがん免疫療法の現状と今後の展開 (2019)
  • Author(s): 西川博嘉
  • Organizer: 第119回日本 外科学会定期学術集会
• [Presentation] The association of genomic features and immunosuppression in gastric cancer (2019)
  • Author(s): Kumagai S, Togashi Y, Shitara K, Tsuchihara K, Nishikawa H
  • Organizer: AACR Annual Meeting 2019
  • Int'l Joint Research
• [Presentation] The secondary immune selection is the dominant mechanism for acquired resistance against adoptive cell therapy (2019)
  • Author(s): Kamada T, Togashi Y, Ohue Y, Nishikawa H
  • Organizer: AACR Annual Meeting 2019
  • Int'l Joint Research
• [Book] Reprogramming the Tumor Microenvironment to Improve Immunotherapy: Emerging Strategies and Combination Therapies (2019)
  • Author(s): Datta M, Coussens LM, Nishikawa H, Hodi FS, Jain RK
  • Total Pages: 165-174
  • Publisher: American Society of Clinical Oncology Educational Book
• [Book] 免疫・炎症病態X治療Update (2019)
  • Author(s): 熊ノ郷淳，西川博嘉 他
  • Total Pages: 252貢
  • Publisher: 南山堂
  • ISBN: 978-4-525-16781-3
• [Remarks] 名古屋大学大学院医学研究科 微生物・免疫学講座 分子細胞免疫学ホームページ
  • URL: https://www.med.nagoya-u.ac.jp/medical_J/laboratory/basic-med/micro-immunology/immunology/
• [Patent(Industrial Property Rights)] 試料保存用組成物 (2020)
  • Inventor(s): 西川 博嘉
  • Industrial Property Rights Holder: 西川 博嘉
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: PCT/JP2020/005991
• [Patent(Industrial Property Rights)] 免疫チェックポイント阻害薬の有効性判定バイオマーカー (2019)
  • Inventor(s): 西川 博嘉
  • Industrial Property Rights Holder: 西川 博嘉
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2019-216881 (JP)
• [Patent(Industrial Property Rights)] がん免疫療法等における免疫関連有害事象の予測 (2019)
  • Inventor(s): 西川 博嘉
  • Industrial Property Rights Holder: 西川 博嘉
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2019-160887（JP）
• [Patent(Industrial Property Rights)] がん細胞を特異的に攻撃しているＴ細胞を同定するための特異的マーカー (2019)
  • Inventor(s): 西川 博嘉
  • Industrial Property Rights Holder: 西川 博嘉
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2019-128517(JP)
• [Patent(Industrial Property Rights)] 免疫チェックポイント阻害薬の有効性判定バイオマーカー (2019)
  • Inventor(s): 西川 博嘉
  • Industrial Property Rights Holder: 西川 博嘉
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: PCT/JP2019/021633（WO)