Immunological assay for development of a novel treatment guideline in malignant melanoma

• Project/Area Number: 16K15551
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Nagoya University
• Principal Investigator: Nishikawa Hiroyoshi 名古屋大学, 医学系研究科, 教授 (10444431)
• Co-Investigator(Renkei-kenkyūsha): YAMAZAKI Naoya 国立がん研究センター中央病院, 皮膚腫瘍科, 科長 (70501873)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: がん免疫療法 / CD4+ T 細胞 / 制御性T細胞 / CD4+T細胞 / 免疫療法 / 免疫制御 / 免疫学 / トランスレーショナルリサーチ

Outline of Final Research Achievements

In this study, immunological responses associated with clinical responses by immune checkpoint inhibitors, particularly anti-PD-1 monoclonal antibodies (mAb) were investigated. Comprehensive analyses by CyTOF with peripheral blood samples revealed that the increase of CD27+Fas-CD4+ central memory T cells after anti-PD-1 mAb treatment was associated with favorable clinical courses. Additionally, the balance of immune responses in tumors corresponded to clinical responses; high effector CD8+ T cells in responders and high immune suppressive CD4+ regulatory T cells in non-responders, respectively. Prospective studies with larger cohorts should be the next step for developing a new treatment guideline.

Research Products

• [Journal Article] Clinical response to PD-1 blockade correlates with a sub-fraction of peripheral central memory CD4+ T cells in patients with malignant melanoma. (2017)
  • Author(s): Takeuchi Y, Tanemura A, Tada Y, Katayama I, Kumanogoh A, Nishikawa H.
  • Journal Title: International Immunology Volume: 30 Issue: 1 Pages: 13-22
  • DOI: 10.1093/intimm/dxx073
  • Peer Reviewed
• [Journal Article] Suppression from beyond the grave (2017)
  • Author(s): Togashi Yosuke、Nishikawa Hiroyoshi
  • Journal Title: Nature Immunology Volume: 18 Issue: 12 Pages: 1285-1286
  • DOI: 10.1038/ni.3870
  • Peer Reviewed
• [Journal Article] Efficacy and safety of autologous peripheral blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: A study protocol for a multicenter exploratory prospective study (Auto-Ph17 study). (2017)
  • Author(s): Nishiwaki S, Sugiura I, Miyata Y, Saito S, Sawa M, Nishida T, Miyamura K, Kuwatsuka Y, Kohno A, Yuge M, Kasai M, Iida H, Kurahashi S, Osaki M, Goto T, Terakura S, Murata M, Nishikawa H, Kiyoi H
  • Journal Title: Medicine Volume: 96 Issue: 52 Pages: e9568-e9568
  • DOI: 10.1097/md.0000000000009568
  • Peer Reviewed / Open Access
• [Journal Article] Regulatory T cells, as a target in anticancer immunotherapy. (2017)
  • Author(s): Enokida T, Nishikawa H
  • Journal Title: Immunotherapy. Volume: 9(8) Issue: 8 Pages: 623-627
  • DOI: 10.2217/imt-2017-0057
  • NAID: 40021131599
  • Peer Reviewed / Open Access
• [Journal Article] Regulatory T Cells: Molecular and Cellular Basis for Immunoregulation (2017)
  • Author(s): Togashi Yosuke、Nishikawa Hiroyoshi
  • Journal Title: Current Topics Microbiology and Immunology Volume: 410 Pages: 3-27
  • DOI: 10.1007/82_2017_58
  • ISBN: 9783319689289, 9783319689296
  • Peer Reviewed
• [Journal Article] Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation. (2017)
  • Author(s): Doki N, Suyama M, Sasajima S, Ota J, Igarashi A, Mimura I, Morita H, Fujioka Y, Sugiyama D, Nishikawa H, Shimazu Y, Suda W, Takeshita K, Atarashi K, Hattori M, Sato E, Watakabe-Inamoto K, Yoshioka K, Najima Y, Kobayashi T, Kakihana K, Takahashi N, Sakamaki H, Honda K, Ohashi K.
  • Journal Title: Ann Hematol Volume: 96(9) Issue: 9 Pages: 1517-1523
  • DOI: 10.1007/s00277-017-3069-8
  • Peer Reviewed / Open Access
• [Journal Article] NY-ESO-1 Protein Cancer Vaccine With Poly-ICLC and OK-432: Rapid and Strong Induction of NY-ESO-1-specific Immune Responses by Poly-ICLC (2017)
  • Author(s): Takeoka T, Nagase H, Kurose K, Ohue Y, Yamasaki M, Takiguchi S, Sato E, Isobe M, Kanazawa T, Matsumoto M, Iwahori K, Kawashima A, Morimoto-Okazawa A, Nishikawa H, Oka M, Pan L, Venhaus R, Nakayama E, Mori M, Doki Y, Wada H.
  • Journal Title: J Immunother Volume: epub Issue: 4 Pages: 140-147
  • DOI: 10.1097/cji.0000000000000162
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Classification of idiopathic interstitial pneumonias using anti-myxovirus resistance-protein 1 autoantibody (2017)
  • Author(s): Hamano Y, Kida H, Ihara S, Murakami A, Yanagawa M, Ueda K, Honda O, Tripathi LP, Arai T, Hirose M, Hamasaki T, Yano Y, Kimura T, Kato Y, Takamatsu H, Otsuka T, Minami T, Hirata H, Inoue K, Nagatomo I, Takeda Y, Mori M, Nishikawa H, Mizuguchi K, Kijima T, Kitaichi T, Tomiyama N, Inoue Y, Kumanogoh A
  • Journal Title: Scientific Reports Volume: 23 Issue: 1 Pages: 43201-43201
  • DOI: 10.1038/srep43201
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] ICOS+ Foxp3+ TILs in gastric cancer are prognostic markers and effector regulatory T cells associated with Helicobacter pylori. (2017)
  • Author(s): 長瀬 博次
  • Journal Title: Int J Cancer Volume: 140(3) Issue: 3 Pages: 686-695
  • DOI: 10.1002/ijc.30475
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] NY-ESO-1 Protein Cancer Vaccine With Poly-ICLC and OK-432: Rapid and Strong Induction of NY-ESO-1-specific Immune Responses by Poly-ICLC (2017)
  • Author(s): Takeoka T, Nagase H, Kurose K, Ohue Y, Yamasaki M, Takiguchi S, Sato E, Isobe M, Kanazawa T, Matsumoto M, Iwahori K, Kawashima A, Morimoto-Okazawa A, Nishikawa H, Oka M, Pan L, Venhaus R, Nakayama E, Mori M, Doki Y and Wada H.
  • Journal Title: J Immunother Volume: -
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers. (2016)
  • Author(s): Saito, T., Nishikawa, H., Wada, H., Nagano, Y., Sugiyama, D., Atarashi, K., Maeda, Y., Hamaguchi, M., Ohkura, N., Sato, E., Nagase, H., Nishimura, J., Yamamoto, H., Takiguchi, S., Tanoue, T., Suda, W., Morita, H., Hattori, M., Honda, K., Mori, M., Doki, Y., Sakaguchi, S.
  • Journal Title: Nat. Med Volume: 22 Issue: 6 Pages: 679-684
  • DOI: 10.1038/nm.4086
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Roles of regulatory T cells in cancer immunity. (2016)
  • Author(s): Takeuchi Y, Nishikawa H
  • Journal Title: Int Immunol Volume: 28(8) Issue: 8 Pages: 401-409
  • DOI: 10.1093/intimm/dxw025
  • NAID: 120005905585
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Fecal microbiota transplantation for patients with steroid-resistant/dependent acute graft-versus-host disease of the gut. (2016)
  • Author(s): KakihanaK,FujiokaY,SudaW,NajimaY,KuwataG,SasajimaS,MimuraI,MoritaH,SugiyamaD,NishikawaH,Hattori M, Hino Y, Ikegawa S, Yamamoto K, Toya T, Doki N, Koizumi K, Honda K, Ohashi K
  • Journal Title: Blood Volume: 128(16) Pages: 2083-2088
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Antibody to CMRF35-Like Molecule 2, CD300e A Novel Biomarker Detected in Patients with Fulminant Type 1 Diabetes. (2016)
  • Author(s): Haseda F, Imagawa A, Nishikawa H, Mitsui S, Tsutsumi C, Fujisawa R, Sano H, Murase-Mishiba Y, Terasaki J, Sakaguchi S, Hanafusa T.
  • Journal Title: PLOS ONE Volume: 11 Issue: 8 Pages: e0160576-e0160576
  • DOI: 10.1371/journal.pone.0160576
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia. (2016)
  • Author(s): UreshinoH,ShindoT,NishikawaH,WatanabeN,WatanabeE,SatohN,KitauraK,KitamuraH,DoiK,NagaseK,Kimura H, Samukawa M, Kusunoki S, Miyahara M, Shin-I T, Suzuki R, Sakaguchi S, Kimura S
  • Journal Title: Cancer Immunol Res Volume: 4(8) Pages: 644-649
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Report on the use of nonclinical studies in the regulatory evaluation of oncology drugs (2016)
  • Author(s): Hayakawa Y, Kawada M, Nishikawa H, Ochiya T, Saya H, Seimiya H, Yao Y, Hayashi M, Kai C, Matsuda A, Naoe T, Ohtsu A, Okazaki T, Saji H, Sata M, Sugimura H, Sugiyama Y, Toi M, Irimura T
  • Journal Title: Cancer Sci Volume: 107(2) Issue: 2 Pages: 189-202
  • DOI: 10.1111/cas.12857
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of Novel and Noninvasive Biomarkers of Acute Cellular Rejection After Liver Transplantation by Protein Microarray. (2016)
  • Author(s): Okubo K, Wada H, Tanaka A, Eguchi H, Hamaguchi M, Tomokuni A, Tomimaru Y, Asaoka T, Hama N, Kawamoto K, Kobayashi S, Marubashi S, Nagano H, Sakaguchi N, Nishikawa H, Doki Y, Mori M, Sakaguchi S
  • Journal Title: Transplant Direct. Volume: 2(12)
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Cancer Immunology and Future Direction of Immune(Checkpoint) Therapy (2018)
  • Author(s): 西川博嘉
  • Organizer: JSMO/ASCO Young Oncologist Workshop 2018
  • Int'l Joint Research / Invited
• [Presentation] Targeting immuno-suppressive cancer microenvironment is critical for successful cancer immunotherapy (2017)
  • Author(s): Hiroyoshi Nishikawa
  • Organizer: The 5th International Symposium of Training Plan for Oncology Professionals
  • Place of Presentation: シェラトン都ホテル大阪（大阪府・大阪市)
  • Year and Date: 2017-03-11
  • Int'l Joint Research / Invited
• [Presentation] Targeting FoxP3+ T cells in Cancers; Friends or Foes? (2017)
  • Author(s): Hiroyoshi Nishikawa
  • Organizer: New York Academy of Science; Frontiers in Cancer Immunotherapy
  • Place of Presentation: The New York Academy of Sciences, New York, USA
  • Year and Date: 2017-02-27
  • Int'l Joint Research / Invited
• [Presentation] Role of FoxP3+ T cells in cancer immunology (2017)
  • Author(s): Hiroyoshi Nishikawa
  • Organizer: International Symposium on Immune Diversity and Cancer Therapy Kobe 2017
  • Place of Presentation: 神戸ポートピアホテル（兵庫県・神戸市)
  • Year and Date: 2017-01-26
  • Int'l Joint Research / Invited
• [Presentation] Immuno-genome analyses to decipher anti-tumor immune responses (2017)
  • Author(s): 西川博嘉
  • Organizer: The 22nd Japanese Foundation for Cancer Research International Symposium on Cancer Chemotherapy
  • Int'l Joint Research / Invited
• [Presentation] がん微小環境における免疫抑制機構 (2017)
  • Author(s): 西川博嘉
  • Organizer: 第58回日本肺癌学会学術集会
  • Invited
• [Presentation] Immune suppressive mechanisms as a target of effective cancer immunotherapy (2017)
  • Author(s): 西川博嘉
  • Organizer: 第76回日本癌学会学術集会
  • Invited
• [Presentation] Immune suppression in tumor microenvironment (2017)
  • Author(s): 西川博嘉
  • Organizer: 第76回日本癌学会学術集会
  • Invited
• [Presentation] How do we target the immunosuppressive cancer microenvironment? (2017)
  • Author(s): 西川博嘉
  • Organizer: 第15回日本臨床腫瘍学会学術集会
  • Invited
• [Presentation] The role of FoxP3+ T cells in colorectal cancer (2017)
  • Author(s): 西川博嘉
  • Organizer: 第15回日本臨床腫瘍学会学術集会
  • Invited
• [Presentation] がん免疫における制御性T細胞の役割 (2017)
  • Author(s): 西川博嘉
  • Organizer: 第38回日本炎症・再生医学会
  • Int'l Joint Research / Invited
• [Presentation] 肺癌に対する免疫応答解析と免疫療法への展開 (2017)
  • Author(s): 西川博嘉
  • Organizer: 第225回日本呼吸器学会関東地方会
  • Invited
• [Presentation] がん微小環境に着目した新たながん免疫療法 (2017)
  • Author(s): 西川博嘉
  • Organizer: 第53回日本肝癌研究会
  • Invited
• [Presentation] 免疫チェックポイント阻害剤の基礎 (2017)
  • Author(s): 西川博嘉
  • Organizer: 第33回日本皮膚悪性腫瘍学会
  • Invited
• [Presentation] Immune suppressive microenvironment in cancer tissues (2017)
  • Author(s): 西川博嘉
  • Organizer: 第21回日本がん免疫学会
  • Invited
• [Presentation] Complexity of immune suppressive microenvironment in cancers (2017)
  • Author(s): 西川博嘉
  • Organizer: The 36th Sapporo International Cancer Symposium
  • Int'l Joint Research / Invited
• [Presentation] がん局所の免疫抑制機構での制御性T細胞の役割 (2017)
  • Author(s): 西川博嘉
  • Organizer: 第21回日本がん分子標的治療学会
  • Invited
• [Presentation] Targeting immuo-suppressive cancer microenvironment for successful cancer immunotherapy (2017)
  • Author(s): 西川博嘉
  • Organizer: 第6回アジア太平洋肝胆膵学会
  • Int'l Joint Research / Invited
• [Presentation] がん免疫分野とがん免疫療法の近年の進歩 (2017)
  • Author(s): 西川博嘉
  • Organizer: 第29回日本内分泌外科学会
  • Invited
• [Presentation] がん免疫療法の効果促進に向けた試み (2017)
  • Author(s): 西川博嘉
  • Organizer: 日本癌学会市民公開講座
  • Invited
• [Presentation] 腫瘍免疫の基礎（新たな薬剤の開発に向けて） (2017)
  • Author(s): 西川博嘉
  • Organizer: 第116回日本皮膚科学会総会
  • Invited
• [Presentation] がん免疫に関与するがん微小環境 (2017)
  • Author(s): 西川博嘉
  • Organizer: 第57回日本呼吸器学会学術講演会
  • Invited
• [Presentation] がん微小環境における免疫抑制機構 (2017)
  • Author(s): 西川博嘉
  • Organizer: 第54回日本臨床分子医学会学術集会
  • Invited
• [Presentation] EGFR遺伝子変異陽性非小細胞肺癌で細胞障害性Tリンパ球浸潤が減少する分子学的機序 (2016)
  • Author(s): 竹内美子・冨樫庸介・杉山栄里・木島貴志・熊ノ郷淳・新谷康・奥村明之進・青景圭樹・菱田智之・石井源一郎・坪井正博・西川博嘉,
  • Organizer: 第57回日本肺癌学会
  • Place of Presentation: 福岡国際会議場（福岡県・福岡市）
  • Year and Date: 2016-12-19
• [Presentation] Control of regulatory T cells for effective cancer immunotherapy (2016)
  • Author(s): Hiroyoshi Nishikawa
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県・宜野湾市）
  • Year and Date: 2016-12-05
  • Invited
• [Presentation] The next steps of immune checkpoint inhibitors (2016)
  • Author(s): Hiroyoshi Nishikawa
  • Organizer: 第29回日本放射線腫瘍学会
  • Place of Presentation: 国立京都国際会館（京都府・京都市）
  • Year and Date: 2016-11-25
  • Invited
• [Presentation] がん免疫療法におけるprecision medicine (2016)
  • Author(s): 西川博嘉
  • Organizer: 第75回日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市)
  • Year and Date: 2016-10-06
  • Invited
• [Presentation] Regulatory T-cell induced anergic CD8+ T cells with suppressive function are novel targets of anti-CTLA-4 mAb (2016)
  • Author(s): Danbee Ha, Hiroyoshi Nishikawa, Daisuke Sugiyama, Yuka Maeda, Dennis Adeegbe, Eichi Sato, Atsushi Tanemura, Ichiro Katayama, Shimon Sakaguchi
  • Organizer: 第75回日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市)
  • Year and Date: 2016-10-06
• [Presentation] Perspective of T cell responses as prodictive markers in cancer immunotherapy, (2016)
  • Author(s): Yuka Maeda, Hiroyoshi Nishikawa, Hiroyuki Mano
  • Organizer: 第75回日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市)
  • Year and Date: 2016-10-06
  • Invited
• [Presentation] がん患者における免疫病態の最新知見とがん治療への応用 (2016)
  • Author(s): 西川博嘉
  • Organizer: 第44回日本臨床免疫学会
  • Place of Presentation: 京王プラザホテル（東京都・新宿区）
  • Year and Date: 2016-09-08
  • Invited
• [Presentation] Regulatory T cells as a target of cancer immunotherapy, (2016)
  • Author(s): 西川博嘉
  • Organizer: 第14回日本臨床腫瘍学会
  • Place of Presentation: 神戸国際展示場（兵庫県・神戸市)
  • Year and Date: 2016-07-28
  • Invited
• [Presentation] がん免疫療法でのバイオマーカーとしての免疫抑制細胞 (2016)
  • Author(s): 西川博嘉
  • Organizer: 第20回日本がん免疫学会
  • Place of Presentation: 大阪国際交流センター（大阪府・大阪市)
  • Year and Date: 2016-07-27
  • Invited
• [Presentation] Critical Role of Regulatory T cells in Cancer Immunotherapy for Hematologic Malignancies (2016)
  • Author(s): 西川博嘉
  • Organizer: The 5th JCA-AACR Special Joint Conference
  • Place of Presentation: 東京ベイ舞浜ホテル（千葉県・浦安市)
  • Year and Date: 2016-07-13
  • Int'l Joint Research / Invited
• [Presentation] がん免疫療法で誘導される免疫応答と免疫抑制の関連 (2016)
  • Author(s): 西川博嘉
  • Organizer: 第20回日本がん分子標的治療学会
  • Place of Presentation: 別府国際コンベンションセンター（大分県・別府市)
  • Year and Date: 2016-05-30
  • Invited
• [Presentation] Cell-depleting anti-CCR4 mAb therapy (2016)
  • Author(s): 西川博嘉
  • Organizer: The 7th JSH International Symposium
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫県・淡路市)
  • Year and Date: 2016-05-13
  • Int'l Joint Research / Invited
• [Presentation] Cancer Immunotherapy (2016)
  • Author(s): 西川博嘉
  • Organizer: 5th Japan Taiwan Oncology Phase I Trail Conference
  • Place of Presentation: Evergreen International Convention Center, Taipei,Taiwan
  • Int'l Joint Research / Invited
• [Book] がん免疫療法ハンドブック (2016)
  • Author(s): 西川博嘉
  • Total Pages: 223
  • Publisher: メディカルレビュー社
• [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/
• [Remarks] 名古屋大学大学院医学系研究科ホームページ
  • URL: https://www.med.nagoya-u.ac.jp/medical_J/laboratory/basic-med/micro-immunology/immunology/