Elucidation of the immunological escape mechanisms and its application for cancer immunotherapy

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390375
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: YASUMOTO Kosei University of Occupational and Environmental Health, Japan, 医学部, 名誉教授 (30150452)
• Co-Investigator(Kenkyū-buntansha): HANAGIRI Takeshi 産業医科大学, 医学部, 准教授 (30299614) ; TAKENOYAMA Mitsuhiro 産業医科大学, 医学部, 非常勤医師 (10309966) ; BABA Tetsuro 産業医科大学, 医学部, 助教 (10506348) ; SHIGEMATSU Yoshiki 産業医科大学, 医学部, 助教 (10546469) ; ICHIKI Yoshinobu 産業医科大学, 医学部, 助教 (80419837)
• Project Period (FY): 2008 – 2010
• Keywords: 肺癌 / 腫瘍抗原 / 免疫逃避 / 制御性T細胞 / HLA

Research Abstract

It is the important issue to resolve immunological escape mechanisms for the establishment of effective immunotherapies in cancer patients. Regulatory T cells accumulated in draining lymph nodes and the tumor tissue in lung cancer patients. Depletion of regulatory T cells resulted in the successful induction of CTL in vitro. By restoration of HLA class I expression on tumor cells, we could identify the antigen that may be associated with immunoediting. Finally, to solve the difficulties in the induction of CTL in immunosuppresive cancer patients, we succeeded in the generation of gd cells specific for tumor cell in vitro and in vivo by transducing the engineered T cell receptor specific for tumor antigen.

Research Products

• [Journal Article] Identification of a lung cancer antigen evading CTL attack due to loss of human leukocyte antigen (HLA) class I expression. (2010)
  • Author(s): Baba T, Hanagiri T, Takenoyama M, Shiota H, Shigematsu Y, Ichiki Y, Uramoto H, So T, Yasumoto K
  • Journal Title: Cancer Sci 101 Pages: 2115-2120
  • Peer Reviewed
• [Journal Article] Tumor antigens and serological biomarkers for the diagnosis of asbestos-related malignancies. (2010)
  • Author(s): Yasuda M, Hanagiri T, Takenoyama M, Yasumoto K
  • Journal Title: Curr Res in Cancer 4 Pages: 39-40
  • Peer Reviewed
• [Journal Article] 悪性胸膜中皮腫の治療経験 (2010)
  • Author(s): 浦本秀隆,下川秀彦,馬場哲郎,重松義紀,永田好香,小野憲司,竹之山光広,花桐武志
  • Journal Title: J UOEH 32 Pages: 257-264
  • Peer Reviewed
• [Journal Article] Correlation between HLA alleles and EGFR mutation in Japanese patients with adenocarcinoma of the lung. (2010)
  • Author(s): Uramoto H, So T, Nagata Y, Kuroda K, Shigematsu Y, Baba T, So T, Takenoyama M, Hanagiri T, Yasumoto K
  • Journal Title: J Thorac Oncol 5 Pages: 1136-1142
  • Peer Reviewed
• [Journal Article] Identification of a tumour associated antigen in lung cancer patients with asbestos exposure. (2010)
  • Author(s): Yasuda M, Hanagiri T, Shigematsu Y, Onitsuka T, Kuroda K, Baba T, Mizukami M, Ichiki Y, Uramoto H, Takenoyama M, Yasumoto K
  • Journal Title: Anticancer Res 30 Pages: 2631-2639
  • Peer Reviewed
• [Journal Article] Clinical significance of cancer/testis antigens expression in patients with non-small cell lung cancer. (2010)
  • Author(s): Shigematsu Y, Hanagiri T, Shiota H, Kuroda K, Baba T, Mizukami M, So T, Ichiki Y, Yasuda M, So T, Takenoyama M, Yasumoto K
  • Journal Title: Lung Cancer 68 Pages: 105-110
  • Peer Reviewed
• [Journal Article] Identification of ribosomal protein L19 as a novel tumor antigen recognized by autologous cytotoxic T lymphocytes in lung adenocarcinoma. (2010)
  • Author(s): Kuroda K, Takenoyama M, Baba T, Shigematsu Y, Shiota H, Ichiki Y, Yasuda M, Uramoto H, Hanagiri T, Yasumoto K
  • Journal Title: Cancer Sci 101 Pages: 46-53
  • Peer Reviewed
• [Journal Article] 癌免疫療法-最近の話題から- (2009)
  • Author(s): 花桐武志,竹之山光広,安元公正
  • Journal Title: Biotherapy 23 Pages: 401-407
• [Journal Article] Malignant mesothelioma-associated antigens recognized by tumor-infiltrating B cells and the clinical significance of the antibody titers. (2009)
  • Author(s): Shigematsu Y, Hanagiri T, Kuroda K, Baba T, Mizukami M, Ichiki Y, Yasuda M, Takenoyama M, Sugio K, Yasumoto K
  • Journal Title: Cancer Sci 100 Pages: 1326-1334
  • Peer Reviewed
• [Journal Article] Clinical significance of HLA class I alleles on postoperative prognosis of lung cancer patients in Japan. (2009)
  • Author(s): Nagata Y, Hanagiri T, Mizukami M, Kuroda K, Shigematsu Y, Baba T, Ichiki Y, Yasuda M, So T, Takenoyama M, Sugio K, Nagashima A, Yasumoto K
  • Journal Title: Lung Cancer 65 Pages: 91-97
  • Peer Reviewed
• [Journal Article] 肺癌の免疫療法の現況と展望 (2009)
  • Author(s): 花桐武志,竹之山光広,安元公正
  • Journal Title: 呼吸器科 15 Pages: 132-138
• [Journal Article] 選択的ワクチン療法:非特異的免疫療法からの脱出?:現状と展望MAGE抗原を用いた免疫療法の可能性 (2009)
  • Author(s): 花桐武志,杉尾賢二,安元公正
  • Journal Title: Oncology 6 Pages: 72-80
• [Journal Article] Association between estrogen receptor-beta expression and epidermal growth factor receptor mutation in the postoperative prognosis of adenocarcinoma of the lung. (2009)
  • Author(s): Nose N, Sugio K, Oyama T, Nozoe T, Uramoto H, Iwata T, Onitsuka T, Yasumoto K
  • Journal Title: J Clin Oncol 27 Pages: 411-417
  • Peer Reviewed
• [Journal Article] Current status and perspectives on immunotherapy for lung cancer. (2009)
  • Author(s): 花桐武志, 竹之山光広, 安元公正
  • Journal Title: Curr.Res.in Cancer 3 Pages: 75-87
• [Journal Article] Significance of Smoking as a Postoperative Prognostic Factor in Patients with Non-small Cell Lung Cancer. (2008)
  • Author(s): Hanagiri T, Sugio K, Mizukami M, Ichiki Y, Sugaya M, Yasuda M, Takenoyama M, Yasumoto K
  • Journal Title: J Thorac Oncol 3 Pages: 1127-1132
  • Peer Reviewed
• [Presentation] 食道癌におけるHLA classI分子の発現に関する検討 (2010)
  • Author(s): 小野憲司,花桐武志,永田好香,下川秀彦,重松義紀,馬場哲郎,浦本秀隆,竹之山光広,安元公正
  • Organizer: 第48回日本癌治療学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20101028-20101030
• [Presentation] Diagnostic markers for malignatn pleural mesothelinoma : Serum antibody against antigens recognized by antibodies produced from tumor infiltraring B cells. (2010)
  • Author(s): Shigematsu Y, Kuroda K, Baba T, Ichiki Y, Ono K, Yasuda M, Uramoto H, So T, Takenoyama M, Hanagiri T, Yasumoto K
  • Organizer: The 10th International Conferenceoftne International Mesothelinoma Interest Group
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20100831-20100903
• [Presentation] T細胞受容体移入γδT細胞による養子免疫療法への応用 (2010)
  • Author(s): 重松義紀,黒田耕志,馬場哲郎,永田好香,下川秀彦,小野憲司,浦本秀隆,竹之山光広,花桐武志,安元公正
  • Organizer: 第14回日本がん免疫学会総会
  • Place of Presentation: 熊本
  • Year and Date: 20100722-20100723
• [Presentation] T細胞受容体移入γδT細胞による治療効果の検討 (2010)
  • Author(s): 重松義紀,塩田広宣,黒田耕志,馬場哲郎,宗哲哉,小野憲司,浦本秀隆,宗知子,竹之山光広,花桐武志,安元公正
  • Organizer: 第31回癌免疫外科研究会
  • Place of Presentation: 大阪
  • Year and Date: 20100520-20100521
• [Presentation] 局所進行期乳癌に対する術後補助療法としてのHER2蛋白ワクチンの検討 (2010)
  • Author(s): 黒田耕志,竹之山光広,馬場哲郎,重松義紀,宗哲哉,市来嘉伸,小野憲司,安田学,菅谷将一,浦本秀隆,宗知子,花桐武志,安元公正
  • Organizer: 第31回癌免疫外科研究会
  • Place of Presentation: 大阪
  • Year and Date: 20100520-20100521
• [Presentation] 悪性胸膜中皮腫関連抗原の同定と機能解析 (2010)
  • Author(s): 重松義紀,黒田耕志,馬場哲郎,宗哲哉,安田学,小野憲司,浦本秀隆,宗知子,竹之山光広,花桐武志,安元公正
  • Organizer: 第27回日本呼吸器外科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 20100513-20100514
• [Presentation] 肺癌に高発現する新規腫瘍抗原ribosomal protein L19の機能解析 (2010)
  • Author(s): 黒田耕志,竹之山光広,塩田広宣,馬場哲郎,重松義紀,宗哲哉,水上真紀子,市来嘉伸,小野憲司,安田学,菅谷将一,浦本秀隆,宗知子,花桐武志,安元公正
  • Organizer: 第27回日本呼吸器外科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 20100513-20100514
• [Presentation] 癌精巣抗原KK-LC-1を認識するT細胞受容体移入γδT細胞を用いた養子免疫療法への応用 (2010)
  • Author(s): 重松義紀,塩田広宣,黒田耕志,馬場哲郎,宗哲哉,小野憲司,浦本秀隆,宗知子,竹之山光広,花桐武志,安元公正
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20100408-20100410
• [Presentation] 悪性胸膜中皮腫に対する腫瘍特異的免疫応答の解析 (2010)
  • Author(s): 竹之山光広
  • Organizer: 第28回産業医科大学学会総会
  • Place of Presentation: 北九州
  • Year and Date: 2010-10-12
• [Presentation] T細胞受容体移入γδT細胞を用いた特異的癌免疫療法の開発 (2009)
  • Author(s): 重松義紀,塩田広宣,黒田耕志,馬場哲郎,宗哲哉,小野憲司,浦本秀隆,宗知子,竹之山光広,花桐武志,安元公正
  • Organizer: 第63回日本呼吸器学会・日本結核病学会九州支部秋季学術講演会
  • Place of Presentation: 北九州
  • Year and Date: 20091126-20091127
• [Presentation] 新規腫瘍抗原Ribosomal protein L19の発現と機能の解明 (2009)
  • Author(s): 黒田耕志,竹之山光広,宗知子,塩田広宣,馬場哲郎,重松義紀,永田好香,宗哲哉,市来嘉伸,安田学,小野憲司,浦本秀隆,花桐武志,安元公正
  • Organizer: 第63回日本呼吸器学会・日本結核病学会九州支部秋季学術講演会
  • Place of Presentation: 北九州
  • Year and Date: 20091126-20091127
• [Presentation] 腫瘍浸潤B細胞にて同定した悪性中皮腫関連抗原とその抗体価の臨床的意義 (2009)
  • Author(s): 重松義紀,黒田耕志,馬場哲郎,宗哲哉,小野憲司,浦本秀隆,宗知子,竹之山光広,花桐武志,安元公正
  • Organizer: 第63回日本呼吸器学会・日本結核病学会九州支部秋季学術講演会
  • Place of Presentation: 北九州
  • Year and Date: 20091126-20091127
• [Presentation] 肺癌における細胞障害性T細胞が認識する腫瘍抗原の同定 (2009)
  • Author(s): 竹之山光広,花桐武志,宗知子,安田学,市来嘉伸,宗哲哉,永田好香,馬場哲郎,重松義紀,黒田耕志,小野憲司,浦本秀隆,安元公正
  • Organizer: 第62回日本胸部外科学会定期学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20091011-20091014
• [Presentation] Immunotherapy for Lung Cancer. (2009)
  • Author(s): 安元公正
  • Organizer: 11th Meeting of Chinese Lung Cancer
  • Place of Presentation: Tianjin, China
  • Year and Date: 20090827-20090829
• [Presentation] Diagnostic Markers for Malignant Pleural Mesothelioma : Serum Antibody against Antigens Recognized by Antibodies Produced from Tumor Infiltrating B cells. (2009)
  • Author(s): 重松義紀, 安元公正
  • Organizer: 2009 4th China Medicai Biotech Forum
  • Place of Presentation: Dalian, China
  • Year and Date: 20090808-20090810
• [Presentation] Identification of Tumor Associated Antigens Recognized by CTL in Patients with Lung Cancer. (2009)
  • Author(s): 安元公正
  • Organizer: 2009 4thChina Medicai Biotech
  • Place of Presentation: Forum Dailian, China
  • Year and Date: 20090808-20090810
• [Presentation] The identification of tumor antigens associated with asbestos-related lung cancer. (2009)
  • Author(s): Hanagiri T, Yasuda M, Kuroda K, Shigematsu Y, Baba T, So T, Ono K, Uramoto H, So T, Takenoyama M, Yasumoto K
  • Organizer: 13th World Conferenceon Lung Cancer
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20090731-20090804
• [Presentation] 進行乳癌に対する術後アジュバンドとしてのCHP-HER2ワクチンと免疫学的モニタリング (2009)
  • Author(s): 馬場哲郎,黒田耕志,重松義紀,永田好香,宗哲哉,市来嘉伸,宗知子,竹之山光広,花桐武志,安元公正
  • Organizer: 第13回日本がん免疫学会総会
  • Place of Presentation: 北九州
  • Year and Date: 20090624-20090625
• [Presentation] 石綿関連肺癌に対する液性免疫応答の解析 (2009)
  • Author(s): 安田学,花桐武志,黒田耕志,鬼塚貴光,重松義紀,馬場哲郎,永田好香,宗哲哉,小野憲司,浦本秀隆,宗知子,竹之山光広,安元公正
  • Organizer: 第13回日本がん免疫学会総会
  • Place of Presentation: 北九州
  • Year and Date: 20090624-20090625
• [Presentation] HLA発現異常を有する肺癌に対する腫瘍特異的Tリンパ球の解析 (2009)
  • Author(s): 黒田耕志,竹之山光広,馬場哲郎,重松義紀,宗哲哉,市来嘉伸,小野憲司,安田学,浦本秀隆,宗知子,花桐武志,安元公正
  • Organizer: 第13回日本がん免疫学会総会
  • Place of Presentation: 北九州
  • Year and Date: 20090624-20090625
• [Presentation] T細胞受容体移入γδT細胞を用いた特異的癌免疫療法の開発 (2009)
  • Author(s): 重松義紀,塩田広宣,黒田耕志,馬場哲郎,宗哲哉,市来嘉伸,小野憲司,浦本秀隆,宗知子,竹之山光広,花桐武志,安元公正
  • Organizer: 第13回日本がん免疫学会総会
  • Place of Presentation: 北九州
  • Year and Date: 20090624-20090625
• [Presentation] 肺癌における免疫標的の探索と治療への応用 (2009)
  • Author(s): 安元公正
  • Organizer: 第13回日本がん免疫学会総会
  • Place of Presentation: 北九州
  • Year and Date: 20090624-20090625
• [Presentation] HLA class I発現陰性肺癌細胞に対する腫瘍特異的細胞性免疫応答の解析 (2009)
  • Author(s): 黒田耕志,馬場哲郎,竹之山光広,重松義紀,宗哲哉,市来嘉伸,安田学,宗知子,花桐武志,杉尾賢二,安元公正
  • Organizer: 第30回癌免疫外科研究会
  • Place of Presentation: 久留米
  • Year and Date: 20090521-20090522
• [Presentation] 非小細胞肺癌におけるHLA発現と免疫応答の解析 (2009)
  • Author(s): 黒田耕志,塩田広宣,重松義紀,馬場哲郎,水上真紀子,市来嘉伸,安田学,大賀丈史,竹之山光広,花桐武志,杉尾賢二,安元公正
  • Organizer: 第26回日本呼吸器外科学会総会
  • Place of Presentation: 北九州
  • Year and Date: 20090514-20090515
• [Presentation] 肺癌患者の腫瘍特異的免疫応答の解析と免疫療法の構築 (2009)
  • Author(s): 竹之山光広
  • Organizer: 第26回日本呼吸器外科学会総会
  • Place of Presentation: 北九州
  • Year and Date: 20090514-20090515
• [Presentation] 悪性胸膜中皮腫における腫瘍抗原の同定と新規腫瘍マーカーとしての意義 (2009)
  • Author(s): 重松義紀,塩田広宣,黒田耕志,馬場哲郎,永田好香,水上真紀子,市来嘉伸,安田学,竹之山光広,花桐武志,杉尾賢二,安元公正
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20090402-20090404
• [Presentation] 腫瘍抗原特異的T細胞受容体(TCR)遺伝子移入による抗腫瘍エフェクター細胞の誘導(第2報) (2009)
  • Author(s): 竹之山光広,重松義紀,塩田広宣,黒田耕志,馬場哲郎,市来嘉伸,花桐武志,安元公正
  • Organizer: 第62回日本呼吸器学会・日本結核病学会九州支部春季学術講演会
  • Place of Presentation: 那覇
  • Year and Date: 2009-05-23
• [Presentation] 肺癌におけるHLA class I分子の発現と細胞性免疫応答 (2008)
  • Author(s): 黒田耕志,竹之山光広,馬場哲郎,塩田広宣,重松義紀,水上真紀子,市来嘉伸,花桐武志,杉尾賢二,安元公正
  • Organizer: 第21回日本バイオセラピィ学会学術集会総会
  • Place of Presentation: 東京
  • Year and Date: 20081118-20081119
• [Presentation] 腫瘍の免疫逃避機構の解明とその克服 (2008)
  • Author(s): 花桐武志,重松義紀,黒田耕志,馬場哲郎,市来嘉伸,浦本秀隆,大賀丈史,竹之山光広,杉尾賢二,安元公正
  • Organizer: 第21回日本バイオセラピィ学会学術集会総会
  • Place of Presentation: 東京
  • Year and Date: 20081118-20081119
• [Presentation] HLA class I発現を欠失した肺癌症例での新規癌関連抗原の同定 (2008)
  • Author(s): 馬場哲郎,塩田広宣,黒田耕志,重松義紀,水上真紀子,市来嘉伸,竹之山光広,花桐武志,杉尾賢二,安元公正
  • Organizer: 第49回日本肺癌学会総会
  • Place of Presentation: 北九州
  • Year and Date: 20081114-20081115
• [Presentation] 自己肺癌特異的CTL誘導における制御性T細胞の影響 (2008)
  • Author(s): 重松義紀,塩田広宣,黒田耕志,馬場哲郎,永田好香,水上真紀子,市来嘉伸,安田学,竹之山光広,花桐武志,杉尾賢二,安元公正
  • Organizer: 第12回基盤的癌免疫研究会総会
  • Place of Presentation: さいたま
  • Year and Date: 20080702-20080703
• [Presentation] 発現回復させたHLA class I分子に提示される新規肺癌抗原の同定 (2008)
  • Author(s): 馬場哲郎,塩田広宣,黒田耕志,重松義紀,水上真紀子,市来嘉伸,安田学,竹之山光広,花桐武志,杉尾賢二,安元公正
  • Organizer: 第48回日本呼吸器学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 20080615-20080617
• [Presentation] 肺癌所属リンパ節における制御性Tリンパ球の発現と機能解析 (2008)
  • Author(s): 重松義紀,塩田広宣,黒田耕志,馬場哲郎,水上真紀子,市来嘉伸,安田学,竹之山光広,花桐武志,杉尾賢二,安元公正
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎
  • Year and Date: 20080515-20080517
• [Presentation] Immune evasion of lung cancer cells by loss of expression of HLA class I. (2008)
  • Author(s): 安元公正, 花桐武志, 竹之山光広, 馬場哲郎
  • Organizer: 1st European Lung Cancer Conference Geneva
  • Place of Presentation: Switzerland
  • Year and Date: 20080423-20080426