Establishment of evaluation method of tumor immunity for application of immune checkpoint inhibitor to AML/MDS

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09006
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Niigata University
• Principal Investigator: Shibasaki Yasuhiko 新潟大学, 医歯学総合病院, 講師 (50568540)
• Co-Investigator(Kenkyū-buntansha): 成田 美和子 新潟大学, 医歯学系, 教授 (30281009) ; 増子 正義 新潟大学, 医歯学総合病院, 准教授 (70397115)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 腫瘍免疫療法 / MLPC法 / WT1特異的細胞傷害性T細胞

Outline of Final Research Achievements

We recruited patients of myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplastic changes (AML-MRC) in this study. Using paired samples of bone marrow (BM) and peripheral blood (PB), we detected WT1-specific cytotoxic T cell (CTL) clones which were amplified specifically for the WT1 peptide antigen by the MLPC method, and the amount of these clones was evaluated.
Sixty-seven percent of MDS/AML-MRC patients had functional WT1-specific CTL clones in BM. The ratio of CTL clones in BM was about 10 times higher than that in PB. These results show that the site of tumor immunity targeting WT1 is mainly in BM, and there are more patients than previously suggested who might effective for tumor immunotherapy with WT1 peptide vaccines and immune checkpoint inhibitors.

Free Research Field

血液学

Academic Significance and Societal Importance of the Research Achievements

混合リンパ球ペプチド培養法は、WT1ペプチドワクチンや免疫チェックポイント阻害薬などによる腫瘍免疫療法が有効な患者群を抽出する検査法として、有用であることを明らかにした。
WT1をターゲットとした腫瘍免疫の場は主として骨髄であり、WT1ペプチドワクチンや免疫チェックポイント阻害薬による腫瘍免疫療法が有効な症例群が、従来示唆されていた以上に存在する可能性を示した。