The role of fibrocyte in combination treatment of immune checkpoint inhibitor with antiangiogenic agents

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16746
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: The University of Tokushima
• Principal Investigator: MITSUHASHI Atsushi 徳島大学, 大学院医歯薬学研究部(医学域), 特任助教 (00833732)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 免疫チェックポイント阻害薬 / 血管新生阻害薬 / 線維細胞

Outline of Final Research Achievements

Recent clinical trials indicate the combination treatment with immune checkpoint inhibitor and antiangiogenic drug improves the prognosis of lung cancer patients. We focus on the fibrocytes (FCs) as the key mediators of anti-tumor immunity. We investigated the roles of FCs in the combination therapy with dual VEGF and PD-L1 blockade by using subcutaneous mouse model of mesothelioma. Tumor bearing mice were treated with anti-VEGF and anti-PD-L1 antibodies. To evaluate the roles of FCs on the effect of anti-PD-L1 antibody, we implanted the mouse lung FCs near the tumor tissue. Low dose anti-VEGF antibody increased the tumor infiltrated FCs and enhanced the effect of anti-PD-L1 antibody. Mouse FCs expressed PD-L1, and costimulatory molecules CD86. The FCs implantation improved the effect of anti-PD-L1 antibody, and increased the tumor infiltrated CD8+ T cells. The combination blockage of VEGF and PD-L1 has potential to improve the anti-tumor immunity via recruiting the PD-L1+, CD86+ FCs.

Free Research Field

肺がん

Academic Significance and Societal Importance of the Research Achievements

線維細胞(fibrocyte)は良性肺疾患の分野においては疾患病態との関連性が多数報告されているが、悪性腫瘍との関連性について着目した報告は乏しく、腫瘍内fibrocyteの解析を介して新規治療標的の探索も目的とした本研究の学術的意義は高い。今後肺癌治療の第一選択として、免疫チェックポイント阻害薬が血管新生阻害薬や細胞障害性抗癌剤といった既存治療と併用される機会が増加すると予想される。本研究の成果により、これら併用療法の治療効果を予測するバイオマーカーが同定される可能性があり、肺癌診療に与える影響は大きいと考えられる。