Investigation of tumor immune status and development of new immunotherapy for bone and soft tissue sarcoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09198
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kanazawa University
• Principal Investigator: Miwa Shinji 金沢大学, 医学系, 助教 (40753455)
• Co-Investigator(Kenkyū-buntansha): 土屋 弘行 金沢大学, 医学系, 協力研究員 (40227434) ; 武内 章彦 金沢大学, 附属病院, 助教 (70512218) ; 山本 憲男 金沢大学, 医薬保健学総合研究科, 特任教授 (90332668)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肉腫 / 腫瘍免疫 / 免疫療法

Outline of Final Research Achievements

This study enrolled patients with metastatic and/or recurrent sarcomas who underwent DC-based immunotherapy. Patients who were PD-L2 (+) showed lower increases of IFN-γ and IL-12 after DC-based immunotherapy than patients who were PD-L2 (-). The disease control (partial response or stable disease) rates of patients who were PD-L1 (+) and PD-L1 (-) were 0% and 22%, respectively. Disease control rates of patients who were PD-L2 (+) and PD-L2 (-) were 13% and 22%, respectively. Patients who were PD-L1 (+) tumors had significantly poorer overall survival compared with patients who were PD-L1 (-). No associations of HLA class I expression with the immune response or oncological outcomes were observed.
This study suggests that PD-L1 and PD-L2 are promising biomarkers of DC-based immunotherapy, and that addition of immune checkpoint inhibitors to DC-based immunotherapy may improve the outcomes of DC-based immunotherapy.

Free Research Field

骨軟部腫瘍

Academic Significance and Societal Importance of the Research Achievements

骨軟部肉腫における免疫療法では，有効性を示す患者は一部に限られるが，多くの免疫療法は高額の費用を要する．有効性を示す患者を予測する方法，有効性を高める方法が求められる．本研究では，PD-L1，PD-L2の発現が高い患者では樹状細胞療法の有効性が低い傾向がみられた．この結果から，免疫チェックポイントの状態が免疫療法の効果を予測するためのバイオマーカーである可能性，免疫チェックポイントの制御が免疫療法の有効性を高める可能性が示唆された．