Study on establishment of immunotherapy for prostate cancer focusing on CCR4-positive Treg

• Project/Area Number: 18K16715
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Aichi Medical University
• Principal Investigator: WATANABE MASAHITO 愛知医科大学, 医学部, 助教 (50513389)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 前立腺癌 / CCR4 / 制御性T細胞 / 免疫チェックポイント分子 / 免疫チェックポイント

Outline of Final Research Achievements

A total of 15 radical prostatectomy (RP) specimens and 60 biopsy specimens from individuals diagnosed with prostate cancer were analyzed to evaluate the infiltration of CCR4+Tregs in prostate cancer. Moreover, the total number of Tregs, CCR4+Tregs, and T cells and the ratio of CCR4+Tregs to Tregs and T cells in biopsy specimens were compared between patients with poor prognosis who progressed to castration‐resistant prostate cancer (CRPC) within 12 months and those with good prognosis who were stable with hormone‐sensitive prostate cancer over 12 months. Furthermore, biopsy specimens were divided into two groups: low and high CCR4+Treg expression groups and the prognosis was compared between them.
There was a higher expression of CCR4+Tregs in RP specimens with a higher(>=8) Gleason score than in those with a lower (<8) Gleason score. The total number of Tregs and CCR4+Tregs significantly increased in the poor prognosis group.

Academic Significance and Societal Importance of the Research Achievements

進行性前立腺癌に対する有効な治療法の確立は急務であるとされているものの、近年様々な癌腫において有効性が報告されている免疫チェックポイントやサイトカインを介した免疫逃避をターゲットとする免疫治療についてはいまだ未解明である。そういった治療の開発の前段階として、本研究のような前立腺癌組織内における腫瘍免疫について、分子細胞学的に評価することは極めて有用であるものと考えられる。

Research Products

• [Journal Article] Increased infiltration of CCR4-positive regulatory T cells in prostate cancer tissue is associated with a poor prognosis. (2019)
  • Author(s): Watanabe M, Kanao K, Suzuki S, Muramatsu H, Morinaga S, Kajikawa K, Kobayashi I, Nishikawa G, Kato Y, Zennami K, Nakamura K, Tsuzuki T, Yoshikawa K, Ueda R, Sumitomo M.
  • Journal Title: Prostate Volume: 79(14) Issue: 14 Pages: 1658-1665
  • DOI: 10.1002/pros.23890
  • Peer Reviewed / Open Access / Int'l Joint Research