Analysis of antigen presentation mediated with constitutively active autophagy that induced by K-ras mutation

• Project/Area Number: 25871227
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics; Immunology
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: Demachi-Okamura Ayako 愛知県がんセンター(研究所), 腫瘍免疫学部, 主任研究員 (10546948)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: CTL / がん / 免疫 / オートファジー / 膵臓癌 / 腫瘍免疫 / 膵癌 / エピトープ

Outline of Final Research Achievements

The association of K-ras mutation and constitutively active autophagy was investigated. To this end, immortalized normal epithelial cell line was transduced with mutated K-ras gene (G12V). The mutated K-ras-expressing cells had constitutively active autophagosomes. As a results, the cells produced autophagosome-dependent epitopes. These data suggest that the pancreatic cancerous cells having mutated K-ras gene possess tumor-specific antigen presenting machinery.

Research Products

• [Journal Article] Identification of a naturally processed HLA-Cw7-binding peptide that cross-reacts with HLA-A24-restricted ovarian cancer-specific CTLs. (2015)
  • Author(s): Yamada E, Demachi-Okamura A, Kondo S, Akatsuka Y, Suzuki S, Shibata K, Kikkawa F, Kuzushima K.
  • Journal Title: Tissue Antigens Volume: 86(3) Issue: 3 Pages: 164-71
  • DOI: 10.1111/tan.12607
  • Peer Reviewed
• [Journal Article] Induction of HLA-B*40:02-restricted T cells possessing cytotoxic and suppressive functions against haematopoietic progenitor cells from a patient with severe aplastic anaemia. (2015)
  • Author(s): Inaguma Y, Akatsuka Y, Hosokawa K, Maruyama H, Okamoto A, Katagiri T, Shiraishi K, Murayama Y, Tsuzuki-Iba S, Mizutani Y, Nishii C, Yamamoto N, Demachi-Okamura A, Kuzushima K, Ogawa S, Emi N, Nakao S.
  • Journal Title: Br J Haematol. Volume: in press Issue: 1 Pages: 131-134
  • DOI: 10.1111/bjh.13464
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] An HLA-modified ovarian cancer cell line induced CTL responses specific to an epitope derived from claudin-1 presented by HLA-A*24:02 molecules (2013)
  • Author(s): Kondo S, Demachi-Okamura A, Hirosawa T, Maki H, Fujita M, Uemura Y, Akatsuka Y, Yamamoto E, Shibata K, Ino K, Kikkawa F, Kuzushima K.
  • Journal Title: Hum Immunol Volume: 74 Issue: 9 Pages: 1103-1110
  • DOI: 10.1016/j.humimm.2013.06.030
  • Peer Reviewed
• [Presentation] An analysis of TAP-independent epitope created in cancerous cells (2015)
  • Author(s): Ayako Okamura1, Yoshiki Akatsuka, Kiyotaka Kuzushima
  • Organizer: The 74th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 名古屋国際会議場（名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 人工抗原提示細胞を用いたCTLの誘導とがん細胞特異的エピトープ生成過程について (2014)
  • Author(s): 岡村文子，葛島清隆
  • Organizer: 日本がん免疫学会
  • Place of Presentation: ひめぎんホール（松山市）
  • Year and Date: 2014-08-01
  • Invited
• [Presentation] K-rasの活性化変異に伴う高活性オートファジーによるCTLエピトープの産生
  • Author(s): 岡村文子、葛島清隆
  • Organizer: 造血器腫瘍免疫療法研究会
  • Place of Presentation: ウインク愛知（名古屋市）
• [Book] 臨床免疫・アレルギー科 (2014)
  • Author(s): 岡村文子、葛島清隆
  • Total Pages: 4
  • Publisher: 科学評論社
• [Remarks] 人工抗原提示細胞を用いたがん特異的CTLの誘導と新しい腫瘍抗原の同定
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/05shuyo_meneki/index.html#member