Development of therapy for cancer stem cells by cellular immunity using human monocyte-derived iPS cells and PD-L1 inhibitor

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15935
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Fujita Health University
• Principal Investigator: Hiramatsu Noriko 藤田医科大学, 治験・臨床研究支援センター, 技術員 (10802209)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 単球 / iPS細胞 / 樹状細胞 / マクロファージ / リンパ球 / 肺癌 / PD-L1 / IFN-γ

Outline of Final Research Achievements

Addition of tumor cell lysates to dendritic cells derived from human monocyte-derived iPS cells increased the number of cells expressing high levels of HLA-DR protein, one of the antigen-presenting abilities. By co-culturing peripheral blood lymphocytes of the same person there, the amount of IFN-γ in the culture supernatant increased.On the other hand, it was observed that the expression of PD-L1 tends to increase by adding IFN-γ to cell lines with low expression of PD-L1 protein established from biopsy and surgical tissues of clinical non-small cell lung cancer patients.Therefore, it is suggested that coexistence with dendritic cells derived from human monocyte-derived iPS cells, which promote IFN-γ secretion by lymphocytes, may increase PD-L1 expression in lung cancer cells and consequently improve the pharmacological response of PD-L1 inhibitors.

Free Research Field

細胞生物学関連

Academic Significance and Societal Importance of the Research Achievements

本研究成果の学術的意義として、リンパ球のように分化に伴うゲノム情報の不可逆な修飾を受けていない単球由来iPS細胞を用いて、細胞性免疫の観点から免疫チェックポイント阻害剤の薬効と組み合わせることで、癌細胞に対するより強力な細胞傷害効果を発揮できる可能性がある。また、実際に免疫チェックポイント阻害剤が臨床応用されている肺癌において、PD-L1の発現量と癌幹細胞の誘導性や傷害性について検証したことにより、化学療法や放射線治療に耐性を示し、これまで根絶困難であった癌幹細胞に対する効果も期待され、肺癌に対する新規治療法の確立につながる可能性がある。