Analysis of immune escape mechanism in lung cancer : From a variant of abnormality of HLA expression on tumor cells

• Project/Area Number: 18689035
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Thoracic surgery
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: ICHIKI Yoshinobu University of Occupational and Environmental Health, Japan, 医学部, 助教 (80419837)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 免疫学 / 癌 / 肺癌 / HLA / 細胞障害性Tリンパ球 / 抗原 / 腫瘍免疫 / 細胞性免疫 / 免疫逃避機構

Research Abstract

癌細胞はHLAクラスI分子上に腫瘍抗原を提示することで、CTLから認識され攻撃を受ける。この攻撃から逃避するため、癌細胞はHLAクラスI分子を欠失すると考えられる。
そこで、癌細胞に欠失したHLAクラスI分子を再移入したところ、CTLからより強力に攻撃された。すなわち、欠失したHLAクラスI分子に免疫原性の高い腫瘍抗原が提示されていたことが示唆された。この腫瘍抗原を用いたワクチン療法とともに癌細胞へのHLAクラスI分子移入療法の開発を行っていく。

Research Products

• [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: (in press)
• [Journal Article] Clinical significance of HLA class I alleles on postoperative prognosis of lung cancer patients in Japan (2009)
  • Author(s): Nagata Y.
  • Journal Title: Lung Cancer (in press)
  • Peer Reviewed
• [Journal Article] Lack and restoration of sensitivity of lung cancer cells to cellular attack with special reference to expression of human leukocyte antigen class I and/or major histocompatibility complex class I chain related molecules A/B. (2007)
  • Author(s): Baba, T. ・Hanagiri, T.・Ichiki, Y.・Kuroda, K.・Shigematsu, Y.・Mizukami, M.・Sugaya, M.・Takenoyama, M.・Sugio, K.・Yasumoto, K.
  • Journal Title: Cancer Sci 98(11) Pages: 1795-1802
  • NAID: 10020119377
• [Journal Article] Antitumor Effect of Antibody against a SEREX-Defined Antigen (UOEH-LC-1) on Lung Cancer Xenotransplanted into Severe Combined Immunodeficiency Mice (2007)
  • Author(s): Mizukami, M. Hanagiri, T. Yasuda, M. Kuroda, K. Shigematsu, Y. Baba, T. Fukuyama, T. Nagata, Y. So, T. Ichiki, Y. Sugaya, M. So, T. Takenoyama, M. Sugio, K. Yasumoto, K.
  • Journal Title: Cancer Res 67(17) Pages: 8351-8357
• [Journal Article] Cytokine production of lung cancer cell lines: Correlation between their production and the inflammatory/immunological responses both in vivo and in vitro. (2007)
  • Author(s): Fukuyama, T. Ichiki, Y. Yamada, S. Shigematsu, Y. Baba, T. Nagata, Y. Mizukami, M. Sugaya, M. Takenoyama, M. Hanagiri, T. Sugio, K. Yasumoto, K.
  • Journal Title: Cancer Sci 98(7) Pages: 1048-1054
• [Journal Article] Identification of HLA-A24 restricted shared antigen recognized by autologous cytotoxic T lymphocytes from a patient with large cell carcinoma of the lung (2007)
  • Author(s): Sugaya, M. Takenoyama, M. Shigematsu, Y. Baba, T. Fukuyama, T. Nagata, Y. Mizukami, M. So, T. Ichiki, Y. Yasuda, M. So, T. Hanagiri, T. Sugio, K. Yasumoto, K.
  • Journal Title: Int J Cancer 120(5) Pages: 1055-1062
• [Journal Article] Cytokine production of lung cancer cell lines: Correlation between their production and the inflammatory/immunological resposes both in vivo and in vitro. (2007)
  • Author(s): Fukuyama M.
  • Journal Title: Cnacer Sci 98 Pages: 1048-1054
  • Peer Reviewed
• [Journal Article] Lack and restoration of sensitivity of lung cancer cells to cellular attack with special reference to expression of human leukocyte antigen class I and/or major histocompatibility complex class I chain related molecules A/B. (2007)
  • Author(s): Baba T.
  • Journal Title: Cnacer Sci 98 Pages: 1795-1802
  • Peer Reviewed
• [Journal Article] Antigen effect of antibody against a SEREX-defined antigen (UOEH-LC-1) on lung cancer xenotransphanted into severe combined immunodeficiency mice. (2007)
  • Author(s): Mizukami M.
  • Journal Title: Cancer Res 67 Pages: 8351-8357
  • Peer Reviewed
• [Journal Article] Identification of HLA-A24 restricted shared antigen recognized by autologous cytotoxic T lymphocytes from a patient with large cell carcinoma of the lung. (2007)
  • Author(s): Sugaya M.
  • Journal Title: Int. J. Cancer 120 Pages: 1055-1062
• [Journal Article] Antigens recognized by IgG derived from tumor-infiltrating B lymphocytes in human lung cancer (2006)
  • Author(s): Yasuda, M. Mizukami, M. Hanagiri, T. Shigematsu, Y. Fukuyama, T. Nagata, Y. So, T. Ichiki, Y. Sugaya, M. Takenoyama, M. Sugio, K. Yasumoto, K.
  • Journal Title: Anticancer Res 25(5) Pages: 3607-3612
• [Journal Article] Identification of a new cancer/germline gene, KK-LC-1, encoding an antigen recognized by autologous CTL induced on human lung adenocarcinoma (2006)
  • Author(s): Fukuyama, T. Hanagiri, T. Takenoyama, M. Ichiki, Y. Mizukami, M. So, T. Sugaya, M. So, T. Sugio, K. Yasumoto, K.
  • Journal Title: Cancer Res 66(9) Pages: 4922-4928
• [Journal Article] Effect of IgG produced by tumor-infiltrating B lymphocytes on lung tumor growth. (2006)
  • Author(s): Mizukami, M. Hanagiri, T. Shigematsu, Y. Baba, T. Fukuyama, T. Nagata, Y. So, T. Ichiki, Y. Sugaya, M. Yasuda, M. So, T. Takenoyama, M. Sugio, K.Yasumoto, K.
  • Journal Title: Anticancer Res 26(3) Pages: 1827-1832
• [Journal Article] Antigens recognized by IgG derived from-infiltrating B lymphocytes in human lung cancer. (2006)
  • Author(s): Yasuda M.
  • Journal Title: Anticancer Res. 26 Pages: 1055-1062
• [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
• [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
• [Presentation] HLA classI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
• [Presentation] 肺腺癌におけるCTLの認識する新規腫瘍抗原Ribosomal Protein L19の同定. (2008)
  • Author(s): 黒田耕志・竹之山光広・塩田広宣・重松義紀・馬場哲郎・水上真紀子・市来嘉伸・花桐武志・杉尾賢二・安元公正
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Identification of human ribosomal protein L19 as a novel overexpressed tumour antigen recognized by autologous CTL in human lung adenocarcinoma (2008)
  • Author(s): Kuroda, K. Takenoyama, M. Baba, T. Shiota, H. Shigematsu, Y. Mizukami, M. Ichiki, Y. Yasuda, M. Hanagiri, T. Sugio, K. Yasumoto, K.
  • Organizer: 2008 World Cancer Congress
  • Place of Presentation: Geneva, Switzerland.
• [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
• [Presentation] 細胞障害性Tリンパ球が認識する過剰発現肺癌抗原Ribosomal protein L19の同定と発現解析 (2008)
  • Author(s): 黒田耕志・竹之山光広・宗知子・塩田広宣・重松義紀・馬場哲郎・永田好香・水上真紀子・市来嘉伸・安田学・野添忠浩・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
• [Presentation] Immune evasion of lung cancer cells by loss of expression of HLA class I (2008)
  • Author(s): Yasumoto, K
  • Organizer: 1st European Lung Cancer Conference
  • Place of Presentation: Geneva, Switzerland
• [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
  • Organizer: 第48回日本呼吸器学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Identification of human ribosomal protein L19 as a novel overexpressed tumour antigen recognized by autologous CTL in human lung adenocarcinoma (2008)
  • Author(s): Kuroda, K
  • Organizer: 2008 World Cancer Congress
  • Place of Presentation: Geneva, Switzerland
• [Presentation] 肺腺癌におけるCTLの認識する新規腫瘍抗原Ribosomal Protein L19の同定 (2008)
  • Author(s): 黒田耕志
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [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
  • Organizer: 第49回日本肺癌学会総会
  • Place of Presentation: 北九州
• [Presentation] Antitumor effect of antibody againset a novel(UOEH-LC-1)on lung cancer xenotransplanted into SCID mice. (2007)
  • Author(s): Mizukami, M. Hanagiri, T.Yasuda, M.Baba, T.Nagata, Y.Ichiki, Y.Sugaya, M.So, T.Takenoyama, M.Sugio, K.Yasumoto, K.
  • Organizer: 12th World Conference on Lung Cancer.
  • Place of Presentation: Seoul, Korea
• [Presentation] Analysis of the correlation between HLA phenotype and prognosis of non-small cell lung cancer patients in Japan (2007)
  • Author(s): Nagata, Y. ・Kuroda, K.・Shigematsu, Y.・Baba, T.・Fukuyama, T.・Mizukami, M.・So, T.・Ichiki, Y.・Sugaya, M.・Yasuda, M.・So, T.・Takenoyama, M.・Hanagiri, T.・Sugio, K.・Nagashima, A.・Yasumoto, K.:
  • Organizer: 12th World Conference on Lung Cancer
  • Place of Presentation: Seoul, Korea
• [Presentation] Restoration of HLA-class I expression on lung cancer cells and successful induction of CTL against tumor cells (2007)
  • Author(s): Hanagiri, T. ・Baba, T.・Kuroda, K.・Shigematsu, Y.・Nagata, Y.・Mizukami, M.・So, T.・Ichiki, Y.・Sugaya, M.・Yasuda, M.・Nozoe, T.・Takenoyama, M.・Sugio, K.・Yasumoto, K:
  • Organizer: 98th AACR.
  • Place of Presentation: Los Angeles, USA.
• [Presentation] Analysis of humonal immunity of tumor infiltrating B lymphocyte in parients with malignant mesothelioma (2007)
  • Author(s): Shigematsu, Y. ・Hanagiri, T.・Baba, T.・Kuroda, K.・Nagata, Y.・Mizukami, M.・Ichiki, Y.・Sugaya, M.・Yasuda, M.・Nozoe, T.・Takenoyama, M.・Sugio, K.・Yasumoto, K.
  • Organizer: 98th AACR
  • Place of Presentation: Los Angeles, USA
• [Presentation] Evasion of lung cancer cells with HLA-class I abnormality from host defense and exploration of the immunotherapy-strategy againest such cancer cells. (2007)
  • Author(s): Takenoyama, M. ・Baba, T.・Ichiki, Y.・Mizukami, M.・Sugaya, M.・Yasuda, M.・Hanagiri, T.・Sugio, K.・Yasumoto, K:
  • Organizer: Keystone Symposia
  • Place of Presentation: Banff, Canada
• [Presentation] Identifiation of the gene encoding a tumor associated antigen using immortalized T cells transduced with T cell reseptor from the specific CTL clone in a lung cancer patient (2007)
  • Author(s): Baba, T. ・Ichiki, Y.・Mizukami, M.・Sugaya, M.・Yasuda, M.・Takenoyama, M.・Hanagiri, T.・Sugio, K.・Yasumoto, K.
  • Organizer: Keystone Symposia
  • Place of Presentation: Banff, Canada
• [Presentation] Identification of a new cancer/testis antigen and the expression in non-small cell lung cancer (2007)
  • Author(s): Hanagiri, T. ・Fukuyama, T.・Baba, T.・Kuroda, K.・Shigematsu, Y.・Nagata, Y.・Mizukami, M.・Ichiki, Y.・Sugaya, M.・Yasuda, M.・Nozoe, T.・Takenoyama, M.・Sugio, K.・Yasumoto, K.
  • Organizer: First JCA-AACR Special Joint Conference
  • Place of Presentation: Nagoya, Japan
• [Presentation] Restoration of HlA-class I expression on lung cancer cells and successful induction of CTL against tumor cells (2007)
  • Author(s): Hanagiri T.
  • Organizer: 98th American Association for Cancer Research
  • Place of Presentation: Los Angeles, USA
• [Presentation] Identification of a new tumor antigen by using an immortalized T cell receptor gene (2006)
  • Author(s): Ichiki, Y. ・Baba, T.・Hanagiri, T.・Takenoyama, M.・Shigematsu, Y.・Fukuyama, T.・Nagata, Y.・Mizukami, M.・So, T.・Sugaya, M.・So, T.・Sugio, K.・Yasumoto, K.
  • Organizer: 97th Annual Meeting AACR.
  • Place of Presentation: Washington,DC, USA
  • Year and Date: 2006-04-01
• [Presentation] Identification of a new cancer/testis antigen recognized by autologous CTL induced in a patient with lung adenocarcinoma (2006)
  • Author(s): Fukuyama, T. ・Shigematsu, Y.・Baba, T.・Nagata, Y.・Mizukami, M.・So, T.・Ichiki, Y.・Sugaya, M.・So, T.・Takenoyama, M.・Oyama, T.・Hanagiri, T.・Sugio, K.・Yasumoto, K.
  • Organizer: 97th Annual Meeting AACR.
  • Place of Presentation: Washington,DC, USA.
  • Year and Date: 2006-04-01
• [Presentation] HLA haplotype lossを有する肺癌症例における細胞性免疫応答の解析. (2006)
  • Author(s): 市来嘉伸・花桐武志・竹之山光広・黒田耕志・重松義紀・馬場哲郎・福山隆・永田好香・水上真紀子・宗哲哉・安田学・菅谷将一・宗知子・小山倫浩・杉尾賢二・安元公正
  • Organizer: 第47回日本肺癌学会総会.
  • Place of Presentation: 京都