Immune Response to Malignant Cells and its Regulation

2011 Fiscal Year Final Research Report

• Project Area: Immunological Self Recognition and its Disorders
• Project/Area Number: 19059008
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: MINATO Nagahiro 京都大学, 医学研究科, 教授 (40137716)
• Project Period (FY): 2007 – 2011
• Keywords: 自己認識 / 免疫制御 / 胸腺 / 自己免疫病 / 炎症 / がん

Research Abstract

I discovered a novel type of follicular CD4+ T cells that are increased in normal aged animals, termed senescence-associated T (SA-T) cells. SA-T cells showed compromised proliferation but produced massive amounts of osteopontin in response to TCR-stimulation. During leukemia development, there was a robust increase of SA-T cells irrespective of age in association with the progressive immunodepression. The study suggest that the increase of SA-T cells underlie the global immunodepression in senescence and leukemia.

Research Products

• [Journal Article] E2A and CBP/p300 act in synergy topromote chromatin accessibility of the immunoglobulin κ locus (2012)
  • Author(s): Sakamoto, S., Wakae, K., Anzai, Y., Murai, K., Tamaki, N., Miyazaki, M., Myyazaki, K.,Romanow, W.J., Ikawa, T., Kitamura, D.,Yanagihira, I., Minato, N., Murre, C., and Agata, Y
  • Journal Title: J. Immunol Volume: 188(11) Pages: 5547-60
  • DOI: doi:10.404/jimmunol.1002346
• [Journal Article] Increased c-Myc activity and DNA damage inhematopoietic progenitors precede myeloproliferative disease in Spa-1-deficiency (2011)
  • Author(s): Tanaka, H., Tamura, A., Hattori, M., Sekai,M., Hamazaki, Y., and Minato, N
  • Journal Title: Cancer Science Volume: 102 Pages: 784-791
  • DOI: doi:10.1111/j.1349-7006.2011.01850.x
• [Journal Article] Spa-1 (Sipa1) controlsthe invasion and metastasis of human prostatecancers via Rap signal (2011)
  • Author(s): Shimizu Y, Hamazaki Y, Hattori M, Doi K,Terada Y, Kobayashi T, Toda Y, Yamasak T,Inoue T, Kajita Y, Atsushi M, Kamba T, MikamiY, Kamoto T, Yamada T, Ogawa O, Minato Nand Nakamura E
  • Journal Title: Cancer Science Volume: 102 Pages: 828-836
  • DOI: doi:10.1111/j.1349-7006.2011.01876.x
• [Journal Article] Claudin-4 isinduced in thymocytes of late CD4/CD8 doublepositive stage by E2A and promotes abT cellreceptor.mediated positive selection (2011)
  • Author(s): Kawai. K. Hamazaki, Y., Fujita, H., Fujita,A., Sato, T., Moriwaki, K., Furuse, M., Fujimoto,T., Agata, Y. and Minato, N
  • Journal Title: Proc. Nat. Acad. Sci. USA Volume: 108(10) Pages: 4075-4080
  • DOI: Doi:10.1073/pnas.1014178108
• [Journal Article] Anti-PD-1 antibody reduces CD4+ PD-1+ T cells and relieves the lupus-like nephritis of l NZB/W F1mice (2010)
  • Author(s): Kasagi, S, Kawano, S, Okazaki, T, Honjo, T, Morinobu, A, Hatachi, S, Shimatani, K, Tanaka,Y, Minato, N, and Kumagai, S
  • Journal Title: J.Immunol Volume: 184 Pages: 2337-2347
  • DOI: doi:10.4049/jimmunol.0901652
• [Journal Article] Spa-1 (Sipa1) and Rap signaling in leukemia and cancer metastasis. (Review article) (2009)
  • Author(s): Minato, N., and Hattori, M
  • Journal Title: Cancer Science Volume: 100 Pages: 17-23
  • DOI: doi:10.1007/s11748-008-0294-z
• [Journal Article] Rap signaling in normallymphocyte development and leukemia genesis.(Review article) (2009)
  • Author(s): Minato, N
  • Journal Title: Immune Network Volume: 9 Pages: 35-40
  • DOI: doi:10.4110/in.2009.9.2.35
• [Journal Article] Memoryphenotype PD-1+ CD4+ T cells expressing C/EBPa underlie T cell immunodepression in senescence and leukemia (2009)
  • Author(s): Shimatani, K., Nakashima, Y., Hattori, M., Hamazaki, Y., and Minato, N
  • Journal Title: Proc. Nat. Acad. Sci. USA Volume: 106 Pages: 15807-15812
  • DOI: doi:10.1073/pnas.0908805106
• [Journal Article] Development ofNotch-dependent T cell leukemia by deregulatedRap1 signaling (2008)
  • Author(s): Wang, S-F, Aoki, M., Shinozuka, Y.,Nakashima, Y., Tanaka, H., Taniwaki, F., Hattori,M., and Minato, N
  • Journal Title: Blood Volume: 111 Pages: 3011-3016
  • DOI: doi:10.1182/blood-2007-07-103119
• [Journal Article] Structureof the human programmed death (PD)-1 ligand and its complex with PD-1 that inhibits immune responses (2008)
  • Author(s): Lin, D. Y., Tanaka, Y., Iwasaki, M., Gitttis, A. G., Su, H-P., Mikami, B., Okazaki, T., Honjo, T.,Minato, N., and Garboczi, D, N
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 105 Pages: 3011-3016
  • DOI: doi:10.1073/pnas.0712278105
• [Journal Article] Essential role of Rapsignal in pre-TCR mediated b-selection in ab Tcell development (2008)
  • Author(s): Kometani, K, Moriyama, M, Nakashima, Y,Katayama, Y, Wang, S-F, Saito, T, Hattori, Mand Minato, N
  • Journal Title: Blood Volume: 112 Pages: 4565-4573
  • DOI: doi:10.1182/blood-2008-06-164517
• [Journal Article] Rap signaling is crucial for the competence ofIL-7 response and the development of B-lineagecells (2008)
  • Author(s): Katayama, Y., Sekai, M., Hattori, M.,Miyoshi, I., Hamazaki, Y, and Minato, N
  • Journal Title: Blood Volume: 114 Pages: 1768-1775
  • DOI: doi:10.1182/blood-2009-03-213371
• [Journal Article] Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from claudin-expressing cells (2007)
  • Author(s): Hamazaki, Y, Fujita, H, Kobayashi, T, Choi, Y, H. Scott, Matsumoto, M, and Minato, N
  • Journal Title: Nature Immunol Volume: 8 Pages: 304-311
  • DOI: PMID:17277780
• [Journal Article] Regulation of immune responses and hematopoiesis by the Rap1 signal. (Review) (2007)
  • Author(s): Minato, N, K.Kometani, and M.Hattori
  • Journal Title: Adv. Immunol Volume: 93 Pages: 229-264
  • DOI: PMID: 17383543
• [Journal Article] Intestinal tumorsinactivated in TGF-b signaling secrete CCL9 and recruit CCR1+ myeloid cells that help invasion (2007)
  • Author(s): Kitamura, T., Kometani, K., Hashiba, H.,Matsunaga, A., Miyoshi. H., Hosogi, H., Aoki, M.,Oshima, M., Hattori, M., Takabayashi, A., Minato,N., and Taketo, M
  • Journal Title: Nature Gen Volume: 39 Pages: 467-475
  • DOI: PMID:17369830
• [Journal Article] PD-L1 and tumor-infiltratingCD8+ T lymphocytes are independent prognostic factors of human ovarian cancer (2007)
  • Author(s): Hamanishi J., Mandai, M., Iwasaki, M., Okazaki. T., Tanaka, Y., Yamaguchi, K., Higuchi, T., Yagi, H., Takakura, K, Minato, N., Honjo, T., and Fujii, S
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 104 Pages: 3360-3365
  • DOI: PMID:17360651
• [Journal Article] Impaired T lymphocyte trafficking in micedeficient in an actin-nucleating protein mDial (2007)
  • Author(s): Sakata D, Taniguchi H, Yasuda S,Adachi-Morishima A, Hamazaki Y, Nakayama R,Miki T, Minato N, and Narumiya S
  • Journal Title: J. Exp. Med Volume: 204 Pages: 2031-2038
  • DOI: PMID:17682067
• [Journal Article] T cell lineage determination precedes the initiation of TCRb gene rearrangement (2007)
  • Author(s): Masuda, K, Kakugawa, K, Nakayama, T, Minato, N, Katsura, Y, and Kawamoto, H
  • Journal Title: J. Immunol Volume: 179 Pages: 3699-3706
  • DOI: PMID:17785806
• [Journal Article] Role of Rap signal in normal and disordered hematopoiesis (Review article) Exp
  • Author(s): Minato, N
  • Journal Title: Cell. Res Volume: (Epub ahead of print)
  • DOI: doi:pii:S0014-4827(13)00168-7.10.1016/j.yexcr.2013.04.009.
• [Presentation] Rap signaling in normal hematoiesisand hematologic malignancy (2012)
  • Author(s): Minato, N
  • Organizer: IFOM-Kyoto Symposium
  • Place of Presentation: Milan
  • Year and Date: 2012-10-25
• [Presentation] Rap G protein: Biology and roles inmalignancy (2012)
  • Author(s): Minato, N
  • Organizer: Invited Lecture Series
  • Place of Presentation: Stockholm
  • Year and Date: 2012-05-15
• [Presentation] The impact of leukemia on immunesystem (2011)
  • Author(s): Minato, N
  • Organizer: International Symposium ofJapanese Hematology Society
  • Place of Presentation: Yokohama
  • Year and Date: 2011-10-14
• [Presentation] Immunity and malignancy (2011)
  • Author(s): Minato, N
  • Organizer: Forum Science in Japan
  • Place of Presentation: Washington DC
  • Year and Date: 2011-06-20
• [Presentation] Senescence-related T cells; Role insystemic autoimmunity and malignancy (2011)
  • Author(s): Minato, N
  • Organizer: International Conference on Autoimmunity
  • Place of Presentation: Tokyo
  • Year and Date: 2011-04-17
• [Presentation] Lymphoid stree-surveillanceresponse (2010)
  • Author(s): Minato, N
  • Organizer: International Workshop on Cancer Biology
  • Place of Presentation: Kanazawa
  • Year and Date: 2010-08-28
• [Presentation] gd-T cells and cancerimmunotherapy (2009)
  • Author(s): Minato, N
  • Organizer: International Symposium of Japanese Immunology Society
  • Place of Presentation: Kobe
  • Year and Date: 2009-12-04
• [Presentation] Rap GTPase in normal lymphohematopoiesis and leukemia (2009)
  • Author(s): Minato, N
  • Organizer: Invited Lecture Series
  • Place of Presentation: China
  • Year and Date: 2009-11-02
• [Presentation] Memory phenotype PD-1 CD4 Tcells expressing C/EBPs underlies the global Tcell immunodepression in senescence andmalignancy (2009)
  • Author(s): Minato, N
  • Organizer: International KTCC Worshop
  • Place of Presentation: Kyoto
  • Year and Date: 2009-06-01
• [Book] Rap1 and Spa-1, "Encyclopedia of Cancer" the second edition (2008)
  • Author(s): Minato, N
  • Total Pages: 2540-2544
  • Publisher: Springer Press