New targeted therapy on SOCS1-related immune-response in triple-negative breast cancer

• Project/Area Number: 18K08551
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kyorin University
• Principal Investigator: IMOTO SHIGERU 杏林大学, 医学部, 教授 (10193690)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 乳癌 / SOCS1 / 術前化学療法 / トリプルネガティブ乳癌 / 腫瘍宿主免疫応答 / miRNA

Outline of Final Research Achievements

MicroRNA subset was compared in triple-negative breast cancer (TNBC) and non-TNBC, and SOCS1 (suppressor of cytokine signaling 1) was predicted as interactive targets of miRNA in TNBC. Then, we also examined the targeted gene in cancer tissues by real-time qPCR. Tissues samples were obtained from 146 breast cancer patients with TNBC or non-TNBC. SOCS1 gene amplification was not significantly but relatively lower in TNBC than in non-TNBC. In addition, among 17 cases treated with neoadjuvant chemotherapy, it was relatively lower in 6 chemo-sensitive cases than in 11 chemo-resistant cases. SOCS1 is a negative regulator of JAK-STAT pathway and related to suppression of T cell activation. Our data suggests that down regulation of SOCS1 gene influences clinical benefit of chemotherapy as well as host immune response. Thus, SOCS1 is a promising molecular target to modulate immune editing in TNBC.

Academic Significance and Societal Importance of the Research Achievements

TNBCに対する薬物療法としてPARP阻害薬や免疫チェックポイント阻害薬など有効であるが、再発後の予後は依然として不良である。SOCS1はサイトカインシグナル（JAK-STAT経路）の負の制御分子であり、JAKに直接結合してその機能を抑制する。SOCS1は、TNBCにおいて、CTLA4, PD1に加わる第3の腫瘍免疫抑制因子であることが疑われるため、標的とした創薬に繋がる可能性がある。

Research Products

• [Presentation] New targeted therapy on SOCS1-related immune-response in triple-negative breast cancer (2020)
  • Author(s): Imoto S, Chiba T, Asaga S, Isaka H, Yokoi S, Ishizaka Y, Tsuchiya A, Kamma H
  • Organizer: AACR
• [Presentation] トリプルネガティブ乳癌におけるSOCS1関連免疫応答を標的とした新たな治療戦略 (2020)
  • Author(s): 井本 滋, 千葉 知宏, 麻賀 創太
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] New targeted therapy on SOCS1-related immune-response in triple-negative breast cancer (2020)
  • Author(s): Shigeru Imoto, Tomohiro Chiba, Sota Asaga, Hirotsugu Isaka, Shigehiro Yokoi, Yoshiharu Ishizaka, Ai Tsuchiya, Hiroshi Kamma
  • Organizer: AACR 2020 Poster Session #1709
  • Int'l Joint Research