Analysis of anti-tumor immune mechanisms involved in the pathogenesis of multiple myeloma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08743
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kindai University
• Principal Investigator: Tanaka Hirokazu 近畿大学, 医学部, 臨床教授 (40360846)
• Co-Investigator(Kenkyū-buntansha): 松村 到 近畿大学, 医学部, 教授 (00294083) ; 頼 晋也 近畿大学, 医学部, 講師 (70460855) ; 森田 泰慶 近畿大学, 医学部, 准教授 (80411594)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 多発性骨髄腫 / 骨髄微小環境 / 腫瘍免疫

Outline of Final Research Achievements

The purpose of this study was to analyze the expression of immune checkpoint molecules in MM (stem) cells and to characterize the cells responsible for anti-myeloma immunity, and to elucidate the anti-tumor immune mechanism in MM. We found that the expression of immunosuppressive molecules was significantly higher in the stem cell fraction and stronger in relapsed refractory cases than in newly diagnosed cases. A histologic comparison of immune cells in the stem cell population revealed that suppressive cells were induced more in the stem cell population of resistant cases. In addition, immune checkpoint molecules expressed in the stem cell fraction suppressed cytotoxic activity in co-cultures of tumor cells and immune cells, but not specific molecules, indicating that molecules involved in immune suppression differ from case to case. These results provide a useful foundation for future therapeutic strategies targeting anti-myeloma immunity.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

近年、種々がんに対して免疫チェックポイント分子を標的とした治療法が実用化されているが、骨髄腫では、抗PD-1抗体単剤ではほとんど効果が認められていない。この一因として各免疫チェックポイント分子の発現、および機能が症例ごと、さらには病期により異なっていることが明らかとなり、この成果は今後抗骨髄腫免疫を標的とした治療戦略を構築する上で有用な基盤となる。