Analysis of suppressive mechanisms by regulatory T cells

2013 Fiscal Year Final Research Report

• Project/Area Number: 23300354
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor immunology
• Research Institution: Osaka University
• Principal Investigator: NISHIKAWA Hiroyoshi 大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (10444431)
• Co-Investigator(Renkei-kenkyūsha): DOKI Yuichiro 大阪大学, 大学院・医学系研究科, 教授 (20291445) ; TANEMURA Atsushi 大阪大学, 大学院・医学系研究科, 助教 (50457016)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 癌 / 制御性T細胞 / 抗腫瘍免疫応答

Research Abstract

The phenotypes and characteristics of regulatory T (Treg) cells in tumors were investigated. Treg cells infiltrating into tumors exhibited effector Treg-cell phenotypes and highly expressed CC chemokine receptor 4 (CCR4). Selective depletion of effector-type Tregs by targeting CCR4 induced/augmented cancer antigen-specific CD4+ and CD8+ T-cell responses. In addition, analysis of CD8+ T cells suppressed by Treg cells an unveiled hitherto undefined T-cell phenotype, suggesting a novel mechanism of Treg-cell suppression.

Research Products

• [Journal Article] Regulatory T cells in cancer immunotherapy (2014)
  • Author(s): Nishikawa H, Sakaguchi S
  • Journal Title: Curr Opin Immunol Volume: 27 Pages: 1-7
  • DOI: 10.1016/j.coi.2013.12.005
• [Journal Article] Vaccination With NY-ESO-1 Overlapping Peptides Mixed With Picibanil OK-432 and Montanide ISA-51 in Patients With Cancers Expressing the NY-ESO-1 Antigen (2014)
  • Author(s): Wada H, Isobe M, Kakimi K, Mizote Y, Eikawa S, Sato E, Takigawa N, Kiura K, Tsuji K, Iwatsuki K, Yamasaki M, Miyata H, Matsushita H, Udono H, Seto Y, Yamada K, Nishikawa H, Pan L, Venhaus R, Oka M, Doki Y, Nakayama E.
  • Journal Title: J Immunother Volume: 37(2) Pages: 84-92
  • DOI: 10.1097/CJI.0000000000000017
• [Journal Article] Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking anti-tumor immune responses in humans (2013)
  • Author(s): Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, Ezoe S, Kanakura Y, Sato E, Fukumori Y, Karbach J, Jager E and Shakaguchi S
  • Journal Title: Proc. Natl. Acad Sci USA Volume: 110(44) Pages: 17945-17950
  • DOI: 10.1073/pnas.1316796110
• [Journal Article] Treg induction by a rationally selected Clostridia cocktail from the human microbiota (2013)
  • Author(s): Atarashi K, Tanoue T, Suda W, Oshima K, Nagano Y, Nishikawa H, Fukuda S, Saito T, Narushima S, Hase K, Kim S, Fritz JV, Wilmes P, Ueha S, Matsushima K, Ohno H, Olle B, Sakaguchi S Taniguchi T, Morita H, Hattori M and Honda K
  • Journal Title: Nature Volume: 500 (7461) Pages: 232-236
  • DOI: 10.1038/nature12331
• [Journal Article] Overcoming regulatory T-cell suppression by a lyophilized preparation of Streptococcus pyogenes (2013)
  • Author(s): Hirayama M, Nishikawa H, Nagata Y, Tsuji T, Kato T, Kageyama S, Ueda S, Sugiyama D, Hori S, Sakaguchi S, Ritter G, Old LJ, Gnjatic S, and Shiku H
  • Journal Title: Eur J Immunol Volume: 43 (4) Pages: 989-1000
  • DOI: 10.1002/eji.201242800
• [Journal Article] Natural and induced T regulatory cells in cancer (2013)
  • Author(s): Adeegbe DO, Nishikawa H
  • Journal Title: Frontiers in Immunology Volume: 4 Pages: 190
  • DOI: 10.3389/fimmu.2013.00190
• [Journal Article] Antibody-based therapy in colorectal cancer (2013)
  • Author(s): Noguchi T, Ritter G, Nishikawa H
  • Journal Title: Immunotherapy Volume: 5(5) Pages: 533-545
  • DOI: 10.2217/imt.13.35
• [Journal Article] Establishment of animal models to analyze the kinetics and distribution of human tumor antigen-specific CD8+ T cells (2013)
  • Author(s): Muraoka D, Nishikawa H, Noguchi T, Wang L, Harada N, Sato E, Luescher I, Nakayama E, Kato T, Shiku H
  • Journal Title: Vaccine Volume: 31(17) Pages: 2110-2118
  • DOI: 10.1016/j.vaccine.2013.02.056
• [Journal Article] NY-ESO-1 antibody as a novel tumor marker of gastric cancer (2013)
  • Author(s): Fujiwara S, Wada H, Kawada J, Kawabata R, Takahashi T, Fujita J, Hirao T, Shibata K, Makari Y, Iijima S, Nishikawa H, Jungbluth A, Nakamura Y, Kurokawa Y, Yamasaki M, Miyata H, Nakajima K, Takiguchi S, Nakayama E, Mori M, and Doki Y
  • Journal Title: Br J Cancer Volume: 108 (5) Pages: 1119-1125
  • DOI: 10.1038/bjc.2013.51
• [Journal Article] Manipulation of human early T lymphopoiesis by coculture on human bone marrow stromal cells : Potential utility for adoptive immunotherapy (2013)
  • Author(s): Liu B, Ohishi K, Orito Y, Nakamori Y, Nishikawa H, Ino K, Suzuki K, Matsumoto T, Masuya M, Hamada H, Mineno J, Ono R, Nosaka T, Shiku H, Katayama N
  • Journal Title: Exp Hematol Volume: 41(4) Pages: 367-376
  • DOI: 10.1016/j.exphem.2012.12.001
• [Journal Article] Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-191-110) peptide (2013)
  • Author(s): Eikawa S, Kakimi K, Isobe M, Kuzushima K, Luescher I, Ohue Y, Ikeuchi K, Uenaka A, Nishikawa H, Udono H, Oka M, Nakayama E
  • Journal Title: Int J Cancer Volume: 132(2) Pages: 345-354
  • DOI: 10.1002/ijc.27682
• [Journal Article] Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma (2012)
  • Author(s): Nishikawa H, Maeda Y, Ishida T, Gnjatic S, Sato E, Mori F, Sugiyama D, Ito A, Fukumori Y, Utsunomiya A, Inagaki H, Old LJ, Ueda R and Sakaguchi S
  • Journal Title: Blood Volume: 119 Pages: 3097-3104
  • DOI: 10.1182/blood-2011-09-379982
• [Journal Article] Intracellular tumor-associated antigens represent effective targets for passive immunotherapy (2012)
  • Author(s): Noguchi T, Kato T, Wang L, Maeda Y, Ikeda H, Sato E, Knuth A, Gnjatic S, Ritter G, Sakaguchi S, Old LJ, Shiku H, and Nishikawa H
  • Journal Title: Cancer Res Volume: 72 Pages: 1672-1682
  • DOI: 10.1158/0008-5472.CAN-11-3072
• [Journal Article] Human bone marrow stromal cells simultaneously support B and T/NK lineage development from human haematopoietic progenitors : a principal role for flt3 ligand in lymphopoiesis (2012)
  • Author(s): Nakamori Y, Liu B, Ohishi K, Suzuki K, Ino K, Matsumoto T, Masuya M, Nishikawa H, Shiku H, Hamada H, Katayama N
  • Journal Title: Br J Haematol Volume: 157(6) Pages: 674-686
  • DOI: 10.1111/j.1365-2141.2012.09109.x
• [Journal Article] Clinical Trial of the Intratumoral Administration of Labeled DC Combined With Systemic Chemotherapy for Esophageal Cancer (2012)
  • Author(s): Fujiwara S, Wada H, Miyata H, Kawada J, Kawabata R, Nishikawa H, Gnjatic S, Sedrak C, Sato E, Nakamura Y, Sakakibara M, Kanto T, Shimosegawa E, Hatazawa J, Takahashi T, Kurokawa Y, Yamasaki M, Nakajima K, Takiguchi S, Nakayama E, Mori M, Doki Y
  • Journal Title: J. Immunother Volume: 35(6) Pages: 513-521
  • DOI: 10.1097/CJI.0b013e3182619cb4
• [Journal Article] Tax is a potential molecular target for immunotherapy of adult T-cell leukemia/lymphoma (2012)
  • Author(s): Suzuki S, Masaki A, Ishida T, Ito A, Mori F, Sato F, Narita T, Ri M, Kusumoto S, Komatsu H, Fukumori Y, Nishikawa H, Tanaka Y, Niimi A, Inagaki H, Iida S, Ueda R
  • Journal Title: Cancer Sci Volume: 103(10) Pages: 1764-1773
  • DOI: 10.1111/j.1349-7006.2012.02371.x
• [Journal Article] Peptide-pulsed dendritic cell vaccination targeting interleukin-13 receptor α 2 chain in recurrent malignant glioma patients with HLA-A*24/A*02 allele (2012)
  • Author(s): Iwami K, Shimato S, Ohno M, Okada H, Nakahara N, Sato Y, Yoshida J, Suzuki S, Nishikawa H, Shiku H, Natsume A, Wakabayashi T
  • Journal Title: Cytotherapy Volume: 14 (6) Pages: 733-742
  • DOI: 10.3109/14653249.2012.666633
• [Journal Article] Heteroclitic serological response in esophageal and prostate cancer patients after NY-ESO-1 protein vaccination (2012)
  • Author(s): Kawada J, Wada H, Isobe M, Gnjatic S, Nishikawa H, Jungbluth AA, Okazaki N, Uenaka A, Nakamura Y, Fujiwara S, Mizuno N, Saika T, Ritter E, Yamasaki M, Miyata M, Ritter G, Murphy R, Hoffman EW, Pan L, Old LJ, Doki Y, Nakayama E
  • Journal Title: Int J Cancer Volume: 130 Pages: 584-592
  • DOI: 10.1002/ijc.26074
• [Journal Article] UV irradiation of immunized mice induces type 1 regulatory T cells that suppress tumor antigen specific CTL responses (2011)
  • Author(s): Toda M, Wang L, Ogura S, Torii M, Kurachi M, Kakimi K, Nishikawa H, Matsushima K, Shiku H, Kuribayashi K, Kato T
  • Journal Title: Int J Cancer Volume: 129 Pages: 1126-1136
  • DOI: 10.1002/ijc.25775
• [Presentation] Control of Regulatory T cells in anti-tumor immunity (2014)
  • Author(s): Nishikawa H
  • Organizer: The 29 th Nagoya International Cancer Treatment Symposium シンポジウム
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2014-02-09
• [Presentation] Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+regulatory T cells and augments anti-tumor immune responses in humans (2013)
  • Author(s): Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, Ezoe S, Kanakura Y, Sato E, Fukumori Y, Karbach J, Jager E and Shakaguchi S
  • Organizer: 21st Annual CRI International Cancer Immunotherapy Symposium
  • Place of Presentation: 米国ニューヨーク市
  • Year and Date: 20130930-1002
• [Presentation] エフェクター型制御性T細胞の選択的除去による抗原特異的免疫応答の増強 (2013)
  • Author(s): 杉山大介, 西川博嘉, 前田優香, 西岡めぐみ, 種村 篤, 片山一朗, 江副幸子, 金倉譲, 坂口志文
  • Organizer: 第17回日本がん免疫学会
  • Place of Presentation: 山口県宇部市
  • Year and Date: 20130703-05
• [Presentation] がん免疫における制御性T細胞の役割 (2013)
  • Author(s): 西川博嘉
  • Organizer: 第26回日本バイオセラピィ学会シンポジウム
  • Place of Presentation: 岩手県盛岡市
  • Year and Date: 2013-12-06
• [Presentation] Regulatory T cells : Friends or foes for cancer (2013)
  • Author(s): Nishikawa H
  • Organizer: 18 th Japanese Foundation for Cancer Research International Symposium on Cancer Chemotherapy シンポジウム
  • Place of Presentation: 東京都
  • Year and Date: 2013-12-04
• [Presentation] Selective depletion of effector-type CD4+regulatory T cells efficiently induces anti-tumor immune responses (2013)
  • Author(s): 杉山大介, 西川博嘉, 前田優香, 西岡めぐみ, 種村 篤, 片山一朗, 江副幸子, 金倉譲, 坂口志文
  • Organizer: 第72回日本癌学会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2013-10-04
• [Presentation] NY-ESO-1重複長鎖ペプチドを用いたがんワクチン第1相臨床試験 (2013)
  • Author(s): 西塔卓郎, 和田 尚, 磯部みどり, 垣見和宏, 榮川伸吾, 大植祥弘, 西川博嘉, 森 正樹, 土岐裕一郎, 岡三喜男, 中山睿一
  • Organizer: 第72回日本癌学会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2013-10-04
• [Presentation] NY-ESO-1f ペプチドワクチンによる抗体・ CD4 ・ CD8T細胞免疫応答の誘導 (2013)
  • Author(s): 榮川伸吾, 垣見和宏, 磯部みどり, 和田 尚, 上中明子, 葛島清隆, 西川博嘉, 鵜殿平一郎, 岡三喜男, 中山睿一
  • Organizer: 第72回日本癌学会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2013-10-04
• [Presentation] Treg による免疫抑制の基礎 (2013)
  • Author(s): 西川博嘉
  • Organizer: 第22回日本組織適合性学会 シンポジウム
  • Place of Presentation: 福島県福島市
  • Year and Date: 2013-09-15
• [Presentation] 制御性T細胞を標的としたがん免疫療法 (2013)
  • Author(s): 西川博嘉
  • Organizer: 第29回日本皮膚悪性腫瘍学会シンポジウム
  • Place of Presentation: 山梨県甲府市
  • Year and Date: 2013-08-09
• [Presentation] Potential of combination immunotherapy targeting regulatory T cells (2013)
  • Author(s): Nishikawa H
  • Organizer: Cancer Immunotherapy Consortium
  • Place of Presentation: 米国ワシントン DC
  • Year and Date: 2013-04-25
• [Presentation] Immunosuppression by regulatory T cells in malignant melanoma (2012)
  • Author(s): 前田 優香, 西川 博嘉, 種村 篤, 西岡めぐみ, 杉山 大介, 片山 一朗, 坂口 志文
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2012-12-06
• [Presentation] 成人T細胞白血病患者における免疫応答ー免疫療法への応用の可能性ー (2012)
  • Author(s): 西川博嘉
  • Organizer: 第60回日本ウィルス学会 教育講演
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2012-11-14
• [Presentation] Effects of corticosteroids on tumor immunity induced by CTLA-4 blockade depends on dose and timing (2012)
  • Author(s): Sugiyama D, Maeda Y, Yuan J, Kato T, Sakaguchi S, Shiku H, Old LJ, Wolchok JD, Nishikawa H
  • Organizer: Cancer Immunotherapy
  • Place of Presentation: 米国ニューヨーク市
  • Year and Date: 2012-10-02
• [Presentation] Immunosuppression by regulatory T cells in malignant melanoma (2012)
  • Author(s): Maeda Y, Nishikawa H, Tanemura A, Sugiyama D, Katayama I, Sakaguchi S
  • Organizer: Cancer Immunotherapy
  • Place of Presentation: 米国ニューヨーク市
  • Year and Date: 2012-10-02
• [Presentation] Regulatory T cells in anti-tumor immunity (2012)
  • Author(s): 西川博嘉
  • Organizer: 第71回日本癌学会Lloyd J Oldメモリアルシンポジウム
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2012-09-20
• [Presentation] 制御性T細胞を標的としたがん免疫療法の開発 (2012)
  • Author(s): 西川博嘉
  • Organizer: 第16回日本がん免疫学会 シンポジウム
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2012-07-28
• [Presentation] 抗CTLA-4抗体治療におけるステロイド剤投与量と投与時期の重要性 (2012)
  • Author(s): 前田 優香, 杉山 大介, Jianda Yuan ,加藤 琢磨, 坂口 志文, 珠玖 洋, Lloyd J Old , Jedd D Wolchok, 西川博嘉
  • Organizer: 第16回日本がん免疫学会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2012-07-28
• [Presentation] 制御性T細胞による疾患制御 (2012)
  • Author(s): 西川博嘉,坂口志文
  • Organizer: 第77回日本インターフェロン・サイトカイン学会 シンポジウム
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2012-06-22
• [Presentation] Defining novel targets of immunotherapy for adult T-cell leukemia/lymphoma (2011)
  • Author(s): Maeda Y , Nishikawa H , Ishida T , Sacha G , Mori F , Sugiyama D , Ito A , Old LJ , Ueda R , Sakaguchi S
  • Organizer: The 19th Meeting in the Cancer Research Institute, International Cancer Immunotherapy Symposium Series
  • Place of Presentation: 米国ニューヨーク市
  • Year and Date: 20111003-05
• [Presentation] NY-ESO-1癌ワクチン患者における血清学的「Antigen Spreading」現象 (2011)
  • Author(s): 和田尚, 磯辺みどり, Gnjatic Sacha, 西川博嘉, 上中明子, 中村ゆりか, 藤原進一, 秋武宏規, 山崎誠, 宮田博志, 土岐裕一郎, 中山睿一
  • Organizer: 日本癌学会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 20111003-05
• [Presentation] 術前化学療法を併用した樹状細胞局所投与臨床試験 (2011)
  • Author(s): 藤原進一, 和田尚, 宮田博志, 西川博嘉, 高橋剛, 黒川幸典, 山崎誠, 中島清一, 瀧口修司, 土岐裕一郎, 森正樹
  • Organizer: 日本癌学会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 20111003-05
• [Presentation] プロテインアレイを使用したCHP-MAGEA4ワクチンにより誘導される液性免疫応答の解析 (2011)
  • Author(s): 宮原慶祐, 堀早穂子, 前田優香, 西川博嘉, 上田修吾, 宮本正樹, 五島直樹, 川上和孝, 藤田知信, 河上裕, 池田裕明, 影山慎一, 珠玖洋
  • Organizer: 日本癌学会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 20111003-05
• [Presentation] Comprehensive analyses of humoral and cellular immune responses against cancer/testis antigens in adult T cell leukemia/lymphoma patients (2011)
  • Author(s): Nishikawa H , Maeda Y , Ishida T , Sugiyama D , Ito A , Mori F , Ueda R and Sakaguchi S
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉県千葉市
  • Year and Date: 2011-11-27
• [Presentation] Possible roles of regulatory T cells for the development of exhausted type CD8+ T cells in human melanoma tissue (2011)
  • Author(s): Maeda Y, Nishikawa H, Tanemura A, Sugiyama D, Katayama I, Sakaguchi S
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉県千葉市
  • Year and Date: 2011-11-27
• [Presentation] 成人T細胞性白血病患者における液性免疫応答の網羅的解析 (2011)
  • Author(s): 西川博嘉, 前田優香, 石田高司, 伊藤 旭,森, 芙美子, 上田龍三, 坂口志文
  • Organizer: 日本がん免疫学会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2011-07-01
• [Presentation] 皮膚悪性黒色腫局所における制御性T細胞の免疫抑制機構の解析 (2011)
  • Author(s): 前田優香, 西川博嘉, 種村 篤, 杉山大介, 片山一朗, 坂口志文
  • Organizer: 日本がん免疫学会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2011-07-01
• [Presentation] Regulatory T cells for tumor immunity Science in Japan (2011)
  • Author(s): Nishikawa H
  • Organizer: Forum
  • Place of Presentation: 米国ワシントンDC
  • Year and Date: 2011-06-21
• [Book] 免疫学コア講義 (2012)
  • Author(s): 西川博嘉
  • Publisher: 南山堂
• [Remarks]
  • URL: http://www.ifrec.osaka-u.ac.jp/index.php