Analysis of functional defects in tumor-specific CD4+ T cells in aged animals

• Project/Area Number: 24700994
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor immunology
• Research Institution: Kumamoto University
• Principal Investigator: AWAI Hirotake (TSUKAMOTO Hirotake) 熊本大学, 大学院生命科学研究部, 助教 (10433020)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 免疫老化 / CD4+ T細胞 / IL-6 / Th1 / CD4 T細胞 / 老化 / がん / 免疫療法

Research Abstract

This study demonstrated that systemic increase of IL-6 was an extrinsic factor counteracting tumor-specific Th1 differentiation, and was responsible for the age-associated defect in mounting protective immunity against the tumor in aged animals. Further analysis revealed that IFN-gamma from tumor-specific Th1 cells was indispensable for the beneficial effects of IL-6 blockade on anti-tumor immune responses in aged hosts.

Research Products

• [Journal Article] LY6K-specific CD4^+ T-cell immunity in patients with malignant tumor : Identification of LY6K long peptide encompassing both CD4^+ and CD8^+ T-cell epitopes (2014)
  • Author(s): Tomita Y., Yuno A., Tsukamoto H., Senju S., Kuroda Y., Hirayama M. Irie A., Yatsuda J., Hamada A., Jono H., Yoshida K., Tsunoda T., Daigo Y., Kohrogi H., Yoshitake Y., Nakamura Y., Shinohara M., and Nishimura Y.
  • Journal Title: Oncoimmunology Volume: (In press)
  • Peer Reviewed
• [Journal Article] Identification of CDCA1 long peptides bearing both CD4+ and CD8+ T-cell epitopes : CDCA1-specific CD4+ T-cell immunity in cancer patients (2014)
  • Author(s): Tomita Y., Yuno A., Tsukamoto H., Senju S., Yoshimura S., Osawa R., Kuroda Y., Hirayama M., Hamada A., Jono H., Irie A., Tsunoda T., Kohrogi H., Yoshitake Y., Nakamura Y., Shinohara M., and Nishimura Y.
  • Journal Title: Int. J . Cancer Volume: 134
  • Peer Reviewed
• [Journal Article] LY6K-specific CD4+ T-cell immunity in patients with malignant tumor: Identification of LY6K long peptide encompassing both CD4+ and CD8+ T-cell epitopes. (2014)
  • Author(s): Tomita Y., Yuno A., Tsukamoto H., Senju S., Kuroda Y., Hirayama M. Irie A., Yatsuda J., Hamada A., Jono H., Yoshida K., Tsunoda T., Daigo Y., Kohrogi H., Yoshitake Y., Nakamura Y., Shinohara M., and Nishimura Y.
  • Journal Title: Oncoimmunology Volume: In press
  • Peer Reviewed
• [Journal Article] Identification of CDCA1 long peptides bearing both CD4+ and CD8+ T-cell epitopes: CDCA1-specific CD4+ T-cell immunity in cancer patients. (2014)
  • Author(s): Tomita Y., Yuno A., Tsukamoto H., Senju S., Yoshimura S., Osawa R., Kuroda Y., Hirayama M., Hamada A., Jono H., Irie A., Tsunoda T., Kohrogi H., Yoshitake Y., Nakamura Y., Shinohara M., and Nishimura Y.
  • Journal Title: Int. J. Cancer Volume: 134 Pages: 352-366
  • Peer Reviewed
• [Journal Article] Establishment of HLA-DR4 transgenic mice for the identification of CD4+ T cell epitopes of tumor-associated antigens (2013)
  • Author(s): Yatsuda J., Irie A., Harada K., Michibata Y., Tsukamoto H., Senju S., Tomita Y., Yuno A., Hirayama M., Abu Sayem M., Takeda N., Shibuya I., Sogo S., Fujiki F., Sugiyama H., Eto M. and Nishimura Y.
  • Journal Title: PLoS One Volume: 8
  • Peer Reviewed
• [Journal Article] Myeloid-derived suppressor cells attenuate TH1 development through IL-6 production to promote tumor progression (2013)
  • Author(s): Tsukamoto, H., Nishikata, R., Senju, S., and Nishimura, Y.
  • Journal Title: Cancer. Immunol. Res. Volume: 1 Pages: 64-76
  • Peer Reviewed
• [Journal Article] Identification of promiscuous KIF20A long peptides bearing both CD4+ and CD8+ T-cell epitopes : KIF20A-specific CD4+ T-cell immunity in patients with malignant tumor (2013)
  • Author(s): Tomita Y., Yuno A., Tsukamoto H., Senju S., Kuroda Y., Hirayama M., Irie A., Kawahara K., Yatsuda J., Hamada A., Jono H., Yoshida K., Tsunoda T., Kohrogi H., Yoshitake Y., Nakamura Y., Shinohara M., and Nishimura Y.
  • Journal Title: Clin. Cancer Res. Volume: 15 Pages: 4508-4520
  • Peer Reviewed
• [Journal Article] Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells (2013)
  • Author(s): Horlad, H., Fujiwara, Y., Takemura, K., Ohnishi, K., Ikeda, T., Tsukamoto, H., Mizuta, H., Nishimura, Y., Takeya, M., Komohara, Y.
  • Journal Title: Mol. Nutr. Food Res. Volume: 57 Pages: 1046-1054
  • Peer Reviewed
• [Journal Article] Myeloid-derived suppressor cells attenuate Th1 development through IL-6 during tumor progression. (2013)
  • Author(s): Tsukamoto, H., Nishikata, R., Senju, S. and Nishimura, Y.
  • Journal Title: Cancer. Immunol. Res. Volume: 1 Issue: 1 Pages: 64-76
  • DOI: 10.1158/2326-6066.cir-13-0030
  • Peer Reviewed
• [Journal Article] Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells (2013)
  • Author(s): Horlad Hasita, Fujiwara Yukio, Takemura Kenichi, Ohnishi Koji, Ikeda Tsuyoshi, Tsukamoto Hirotake, Mizuta Hiroshi, Nishimura Yasuharu, Takeya Motohiro, Komohara Yoshihiro
  • Journal Title: Mol. Nutri. Food Res Volume: 57 (6) Issue: 6 Pages: 1-9
  • DOI: 10.1002/mnfr.201200610
  • Peer Reviewed
• [Journal Article] Establishment of HLA-DR4 transgenic mice for the identification of CD4+ T cell epitopes of tumor-associated antigens. (2013)
  • Author(s): Yatsuda J, Irie A, Harada K, Michibata Y, Tsukamoto H, Senju S, Tomita Y, Yuno A, Hirayama M, Abu Sayem M, Takeda N, Shibuya I, Sogo S, Fujiki F, Sugiyama H, Eto M, Nishimura Y.
  • Journal Title: PLoS One Volume: 8 Issue: 12 Pages: e84908-e84908
  • DOI: 10.1371/journal.pone.0084908
  • Peer Reviewed
• [Journal Article] Identification of promiscuous KIF20A long peptides bearing both CD4+ and CD8+ T-cell epitopes: KIF20A-specific CD4+ T-cell immunity in patients with malignant tumor. (2013)
  • Author(s): Tomita, Y.*, Yuno, A.*, Tsukamoto, H., Senju, S., Kuroda, Y., Hirayama, M., Irie, A., Kawahara, K., Yatsuda, J., Hamada, A., Jono, H., Yoshida, K., Tsunoda, T., Kohrogi, H., Yoshitake, Y., Nakamura, Y., Shinohara, M. and Nishimura, Y. (*equal contribution)
  • Journal Title: Clin. Cancer Res Volume: 19 Issue: 16 Pages: 4508-4520
  • DOI: 10.1158/1078-0432.ccr-13-0197
  • Peer Reviewed
• [Journal Article] Myeloid-derived suppressor cells attenuate Th1 development through IL-6 production to promote tumor progression. (2013)
  • Author(s): Tsukamoto, H., Nishikata, R., Senju, S., and Nishimura, Y.
  • Journal Title: Cancer Immunology Research Volume: In press
  • Peer Reviewed
• [Journal Article] Identification of promiscuous KIF20A long peptides bearing both CD4+ and CD8+ T-cell epitopes: KIF20A-specific CD4+ T-cell immunity in patients with malignant tumor. (2013)
  • Author(s): Tomita, Y., Yuno, A., Tsukamoto, H., Senju, S., Kuroda, Y., Hirayama, M., et al.
  • Journal Title: Clinical Cancer Research Volume: submitted
• [Journal Article] Promiscuous LY6K long peptide induces CD4+ T cells and CTLs: LY6K-specific CD4+ T cell immunity augmented by CTL-epitope vaccination in cancer patients. (2013)
  • Author(s): Tomita, Y., Yuno, A., Tsukamoto, H., Senju, S., Kuroda, Y., Hirayama, M. et al.
  • Journal Title: J. Clin. Oncl. Volume: submitted
• [Journal Article] Promiscuous CDCA1 long peptides induce CD4+ T cell and CTLs: CDCA1-specific CD4+ T cell immunity augmented by CTL-epitope vaccination in cancer patients. (2013)
  • Author(s): Tomita, Y., Yuno, A., Tsukamoto, H., Senju, S., Yoshimura, S., Osawa, R., et al.
  • Journal Title: Clinical Cancer Research Volume: submitted
• [Journal Article] Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells. (2013)
  • Author(s): Horlad, H., Fujiwara, Y., Takemura, K., Ohnishi, K., Ikeda, T., Tsukamoto, H., Mizuta, H.,Nishimura, Y., Takeya, M., Komohara, Y.
  • Journal Title: Mol. Nutr. Food Res. Volume: In press
  • Peer Reviewed
• [Presentation] Age-associated increase of IL-6 dampens anti-tumor immune responses through attenuating Th1 differentiation of tumor-specific CD4 T cells (2014)
  • Author(s): Tsukamoto, H., Senju, S., S.L. Swain and Nishimura, Y.
  • Organizer: アメリカ免疫学会
  • Place of Presentation: 米国, Pittsburgh
• [Presentation] Soluble IL-6 receptor diminishes the differentiation of tumor-specific TH1 cells to exacerbate tumor progression (2013)
  • Author(s): Tsukamoto, H., Senju, S., and Nishimura, Y.
  • Organizer: 第42回日本免疫学会
  • Place of Presentation: 千葉、幕張メッセ
• [Presentation] 担癌個体で増加する可溶性IL-6Rは、腫瘍特異的Th1細胞分化の抑制を介して腫瘍増大に寄与する (2013)
  • Author(s): Tsukamoto, H., Senju, S., and Nishimura, Y
  • Organizer: 第17回日本がん免疫学会
  • Place of Presentation: 山口、ANAクラウンプラザホテル宇部
• [Presentation] 担癌個体で増加する可溶性IL-6Rは、 腫瘍特異的Th1細胞の分化抑制を介して腫瘍増大に寄与する (2013)
  • Author(s): 塚本 博丈、千住 覚、西村 泰治
  • Organizer: 日本がん免疫学会
  • Place of Presentation: 山口県宇部市 ANAクラウンプラザホテル
• [Presentation] 担癌個体で増加する可溶性IL-6Rは、腫瘍特異的TH1細胞の分化抑制を介して腫瘍を増大させる (2013)
  • Author(s): Tsukamoto H, Matsumura K, Senju S and Nishimura Y
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉市 幕張メッセ
• [Presentation] Myeloid-derived suppressor cells attenuate Th1 development through IL-6 production to promote tumor progression (2013)
  • Author(s): Tsukamoto H, Senju S and Nishimura Y
  • Organizer: International Congress of Immunology
  • Place of Presentation: イタリア ミラノ
• [Presentation] MDSC attenuate TH1 development of tumor-specific effector CD4 T cells through IL-6 production (2012)
  • Author(s): Tsukamoto, H., Senju, S., and Nishimura, Y.
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 兵庫、神戸国際会議場
• [Presentation] Gr-1+ MDSC attenuate development of tumor-specific Th1 cells through IL-6 production to promote tumor progression (2012)
  • Author(s): Tsukamoto, H., Senju, S., and Nishimura, Y.
  • Organizer: 第16回日本がん免疫学会
  • Place of Presentation: 北海道、北海道大学学術交流会館
• [Presentation] Gr-1+ MDSC attenuate development of tumor-specific Th1 cells through IL-6 production to promote tumor progression. (2012)
  • Author(s): Tsukamoto, H.
  • Organizer: 第１６回 日本がん免疫学会総会
  • Place of Presentation: 北海道大学学術交流会館
• [Presentation] MDSC attenuate Th1 development of tumor-specific effector CD4+ T cells through IL-6 (2012)
  • Author(s): Tsukamoto, H.
  • Organizer: 第１4回 日本免疫学会総会
  • Place of Presentation: 神戸国際会議場
• [Book] 「Myeloid-derived suppressor cells (MDSC)によるTh1細胞の抑制機序」臨床免疫・アレルギー科(61) (2014)
  • Author(s): 塚本博丈
  • Publisher: 科学評論社
• [Book] Myeloid-derived suppressor cells (MDSC)によるTh1細胞の抑制機序 (2014)
  • Author(s): 塚本 博丈
  • Publisher: 科学評論社
• [Book] 「腫瘍免疫の最前線:T細胞を介した抗腫瘍免疫応答」実験医学9月増刊(31) (2013)
  • Author(s): 塚本博丈, 西村泰治
  • Publisher: 羊土社
• [Book] 腫瘍免疫の最前線： T細胞を介した抗腫瘍免疫応答 (2013)
  • Author(s): 塚本 博丈, 西村 泰治
  • Total Pages: 8
  • Publisher: 羊土社