Virus antigen specific CTL in HTLV-1 and EBV associated lymphoma

2016 Fiscal Year Annual Research Report

• Project/Area Number: 26460446
• Research Institution: Kurume University
• Principal Investigator: 大島 孝一 久留米大学, 医学部, 教授 (50203766)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: HTLV-1 / ATLL / TAX / CTL / HLA-A24 / Foxp3

Outline of Annual Research Achievements

HTLV-1ウイルス蛋白であるTAXは、成人T細胞白血病/リンパ腫(ATLL)細胞の増殖に重要な役割を果たし、かつHTLV-1-specific Cytotoxic T lymphocyte(CTL)の標的でもあることが知られている。しかし、HTLV-1-specific CTLがATLL患者のリンパ節の中でどのように作用するかは明らかではない。そこで、ATLLの患者のリンパ節検体を用いて、HLA-A24-restricted TAX-specific CTLの蛍光染色を行い、腫瘍のHLA-A24、TAX、Foxp3の発現との関係を検討した。方法：Assay 1:ATLL患者のリンパ節病変を用いたPCR法にて、HLA-A24を確認したATLLのFrozen sectionを用いて、MHC dextramerによりHLA-A24 restricted　TAX-specific CTLの蛍光染色を行った。Tax-specific CTLとFOXｐ３の関係を解析するため、抗FOXｐ３抗体（Abcam）を使用し免疫染色を行った。また、Tax-specific CTLの活性をみるため、INFγの免疫染色を行っている。その結果、一部の症例で、ATLLのリンパ節病変内にはTax-specific CTLが認められる。また、Tax-specific CTL数は、形態との関連はみられなかったが、FOXｐ3陽性の症例では優位に低い傾向がみられた。このことより、Tregの機能としてCTLを抑制している可能性が示唆された。以上の論文化を行なった。（Ichikawa et al. ONCOLOGY LETTERS 13: 4611-4618, 2017）

Research Products

• [Journal Article] Detection of Tax-specific CTLs in lymph nodes of adult T-cell leukemia/lymphoma patients and its association with Foxp3 positivity of regulatory T-cell function (2017)
  • Author(s): AYAKO ICHIKAWA, HIROAKI MIYOSHI, FUMIKO ARAKAWA, JUNICHI KIYASU, KENSAKU SATO, DAISUKE NIINO, YOSHIZO KIMURA, MAKI YOSHIDA, RIKO KAWANO, HIROKO MUTA, YASUO SUGITA, KOICHI OHSHIMA
  • Journal Title: ONCOLOGY LETTERS Volume: 13 Pages: 4611-4618
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] An Epstein-Barr virus susceptible immature T-cell line, WILL4, established from a patient with T-lymphoblastic lymphoma bearing CD21 and a clonal EBV genome. (2017)
  • Author(s): Hosoi H, Imadome KI, Tamura S, Kuriyama K, Murata S, Yamashita Y, Mushino T, Oiwa T, Kobata H, Nishikawa A, Nakakuma H, Hanaoka N, Isobe Y, Ohshima K, Sonoki T.
  • Journal Title: Leuk Res. Volume: 55 Pages: 1-5
  • Peer Reviewed
• [Journal Article] Composite lymphoma of peripheral T-cell lymphoma and Hodgkin lymphoma, mixed cellularity type; pathological and molecular analysis. (2017)
  • Author(s): Ichikawa A, Miyoshi H, Yamauchi T, Arakawa F, Kawano R, Muta H, Sugita Y, Akashi K, Ohshima K.
  • Journal Title: Pathol Int. Volume: 67 Pages: 194-201.
  • Peer Reviewed
• [Journal Article] Hematopoietic stem cell transplantation in advanced cutaneous T-cell lymphoma. (2017)
  • Author(s): Saruta H, Ohata C, Muto I, Imamura T, Oku E, Ohshima K, Nagafuji K, Nakama T.
  • Journal Title: J Dermatol. Volume: - Pages: -
  • DOI: 10.1111/1346-8138.13848. [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] CCR4 frameshift mutation identifies a distinct group of adult T cell leukaemia/lymphoma with poor prognosis. (2016)
  • Author(s): Yoshida N, Miyoshi H, Kato T, Sakata-Yanagimoto M, Niino D, Taniguchi H, Moriuchi Y, Miyahara M, Kurita D, Sasaki Y, Shimono J, Kawamoto K, Utsunomiya A, Imaizumi Y, Seto M, Ohshima K.
  • Journal Title: J Pathol. Volume: 238 Pages: 621-6
  • Peer Reviewed
• [Journal Article] Analysis of the BRAFV600E mutation in 19 cases of Langerhans cell histiocytosis in Japan. (2016)
  • Author(s): Sasaki Y, Guo Y, Arakawa F, Miyoshi H, Yoshida N, Koga Y, Nakashima K, Kurita D, Niino D, Seto M, Ohshima K.
  • Journal Title: Hematol Oncol Volume: - Pages: -
  • DOI: 10.1002/hon.2293. [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] A Clinicopathologic Study of Lennert Lymphoma and Possible Prognostic Factors: The Importance of Follicular Helper T-cell Markers and the Association With Angioimmunoblastic T-cell Lymphoma. (2016)
  • Author(s): Kurita D, Miyoshi H, Yoshida N, Sasaki Y, Kato S, Niino D, Sugita Y, Hatta Y, Takei M, Makishima M, Ohshima K.
  • Journal Title: Am J Surg Pathol. Volume: 40 Pages: 1249-60.
  • Peer Reviewed
• [Journal Article] New mouse model of acute adult T-cell leukemia generated by transplantation of AKT, BCLxL, and HBZ-transduced T cells (2016)
  • Author(s): Kasugai Y, Yoshida N, Ohshima K, Matsuo K, Seto M, Tsuzuki S.
  • Journal Title: Cancer Sci. Volume: 107 Pages: 1072-8.
  • Peer Reviewed
• [Journal Article] BRAFV600E and MAP2K1 mutations in Langerhans cell histiocytosis occur predominantly in children. (2016)
  • Author(s): Zeng K, Ohshima K, Liu Y, Zhang W, Wang L, Fan L, Li M, Li X, Wang Z, Guo S, Yan Q, Guo Y.
  • Journal Title: Hematol Oncol. Volume: - Pages: -
  • DOI: 10.1002/hon.2344. [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Prognostic Value of Programmed Death Ligand 1 and Programmed Death 1 Expression in Thymic Carcinoma. (2016)
  • Author(s): Yokoyama S, Miyoshi H, Nakashima K, Shimono J, Hashiguchi T, Mitsuoka M, Takamori S, Akagi Y, Ohshima K.
  • Journal Title: Clin Cancer Res. Volume: 22 Pages: 4727-34.
  • Peer Reviewed
• [Journal Article] Clinicopathologic and Prognostic Implications of Programmed Death Ligand 1 Expression in Thymoma. (2016)
  • Author(s): Yokoyama S, Miyoshi H, Nishi T, Hashiguchi T, Mitsuoka M, Takamori S, Akagi Y, Kakuma T, Ohshima K.
  • Journal Title: Ann Thorac Surg. Volume: 101 Pages: 1361-9
  • Peer Reviewed
• [Journal Article] PD-L1 expression on neoplastic or stromal cells is respectively a poor or good prognostic factor for adult T-cell leukemia/lymphoma. (2016)
  • Author(s): Miyoshi H, Kiyasu J, Kato T, Yoshida N, Shimono J, Yokoyama S, Taniguchi H, Sasaki Y, Kurita D, Kawamoto K, Kato K, Imaizumi Y, Seto M, Ohshima K.
  • Journal Title: Blood. Volume: 128 Pages: 1374-81
  • Peer Reviewed
• [Journal Article] MYC translocation and/or BCL 2 protein expression are associated with poor prognosis in diffuse large B-cell lymphoma. (2016)
  • Author(s): Kawamoto K, Miyoshi H, Yoshida N, Nakamura N, Ohshima K, Sone H, Takizawa J.
  • Journal Title: Cancer Sci. 2 Volume: 107 Pages: 853-61
  • Peer Reviewed
• [Journal Article] Six Cases of CD20-Positive Adult T-Cell Leukemia. (2016)
  • Author(s): Kawano R, Niino D, Ohshima K.
  • Journal Title: Clin Exp Hematop. Volume: 56 Pages: 119-125.
  • Peer Reviewed