Study of immunosuppressive tumor microenvironment and therapeutic strategy in breast cancer

• Project/Area Number: 24591925
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kurume University
• Principal Investigator: SEKI Naoko 久留米大学, 医学部, 講師 (40226634)
• Co-Investigator(Kenkyū-buntansha): TOH Uhi 久留米大学, 医学部, 講師 (60268901) ; FUJII Teruhiko 久留米大学, 医学部, 准教授 (50199288) ; KAGE Masayoshi 久留米大学病院, 教授 (80148840)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 癌 / 免疫学 / 乳癌 / 免疫

Outline of Final Research Achievements

Cancer testis (CT)-antigens were expressed in a large proportion of triple negative (TN)- and ALDH-1 positive breast cancer specimens.
NY-ESO-1, MAGE-A10, and MAGE-C1 antigens were immunohistochemically expressed in 6%, 15%, and 12% of patients with primary invasive breast carcinoma, respectively. NY-ESO-1 and MAGE-A10 were preferentially expressed in TN or estrogen receptor negative breast cancers (p<0.05). ALDH-1 expression, which have been reported as predictive marker of cancer stem cells in terms of resistance to chemotherapy, was observed in 22% of tumor specimens, and was most prevalent in the TN breast cancers (p<0.001). Moreover, 41% of ALDH-1 positive specimens were accompanied with expression of any of CT-antigens, some of which showed concomitant expression of CT-antigens and ALDH-1.
Because of the limited therapeutic modalities for these phenotypes, significance of CT-antigens expressions should be further studied for beneficial immunotherapy in breast cancer patients.

Research Products

• [Journal Article] Feasibility study of personalized peptide vaccination for metastatic recurrent triple-negative breast cancer patients. (2014)
  • Author(s): Takahashi R, Toh U, Iwakuma N, Takenaka M, Otsuka H, Furukawa M, Fujii T, Seki N, Kawahara A, Kage M, Matsueda S, Akagi Y, Yamada A, Itoh K, Sasada T.
  • Journal Title: Breast Cancer Res. Volume: 16 Issue: 4 Pages: 00-00
  • DOI: 10.1186/bcr3685
  • Peer Reviewed / Open Access
• [Journal Article] Treatment outcome in patients with stage III breast cancer treated with neoadjuvant chemotherapy. (2013)
  • Author(s): Takahashi R, Toh U, Iwakuma N, Mishima M, Fujii T, Takenaka M, Koura K, Seki N, Kawahara A, Kage M, Ogo E, Shirouzu K
  • Journal Title: Exp Ther Med Volume: 6 Pages: 1089-1095
  • Peer Reviewed
• [Journal Article] FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis (2013)
  • Author(s): Miki Takenaka, Naoko Seki, Uhi Toh, Satoshi Hattori, Akihiko Kawahara, Tomohiko Yamaguchi, Keiko Koura, Ryuji Takahashi, Hiroko Otsuka, Hiroki Takahashi, Nobutaka Iwakuma, Shino Nakagawa, Teruhiko Fujii, Tetsuro Sasada, Rin Yamaguchi, Hirohisa Yano, Kazuo Shirouzu, Masayoshi Kage
  • Journal Title: Molecular and Clinical Oncology Volume: 1 Issue: 4 Pages: 625-632
  • DOI: 10.3892/mco.2013.107
  • Peer Reviewed
• [Presentation] 乳癌におけるCancer/Testis Antigens発現に関する免疫組織学的検討 (2014)
  • Author(s): 竹中 美貴、 関 直子 et al.
  • Organizer: 第22回日本乳癌学会学術総会
  • Place of Presentation: 大阪