Immunotherapy for urothelial cancer focusing on inactive TGFb (LAP) positive immune cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16797
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Murai Ryosuke 滋賀医科大学, 医学部, 非常勤講師 (80748583)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 尿路上皮癌 / 免疫抑制細胞 / LAP陽性細胞 / TGFb

Outline of Final Research Achievements

Examination of LAP (TGFβ) -positive cells using urothelial carcinoma patient specimens: Sample collection was recommended for the examination of LAP-positive cells in urothelial carcinoma patients. Peripheral blood cells on urothelial cancer patients were stained with with anti-CD3, anti-CD4, and anti-LAP antibody, and the proportion of LAP-positive cells in T cells was examined. The proportion of LAP-positive cells ranged from 1% to 10% and was considered to be variable.
Evaluation of activation of peritumor LAP (TGFβ) -positive cells: In order to investigate the presence of LAP-positive cells in clinical specimens, tissue immunostaining of paraffin-embedded sections of bladder cancer tissue was performed with anti-LAP antibody. However, the staining rate was low and effective immunostaining could not be obtained.

Free Research Field

泌尿器癌

Academic Significance and Societal Importance of the Research Achievements

近年、尿路上皮癌に対する癌免疫治療が期待されているが、治療効果は限定的であり、その要因として癌の複雑な免疫逃避機構があげられる。本研究では免疫抑制性サイトカインであるTGFβが免疫細胞表面でLatency associated peptide(LAP)が結合した特徴的な非活性構造（LAP(TGFβ)陽性細胞）をとることに着目した。尿路上皮癌患者の末梢血中および腫瘍組織内のLAP(TGFβ)陽性免疫細胞を詳しく調べ、バイオマーカーとしての意義を検討した。臨床検体を用いたLAP, TGFbの検討を進めることで癌における新たな免疫抑制性システムが解明できると期待される。