A role of AhR signaling in NKT cell based immunotherapy for lung cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16409
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Chiba University
• Principal Investigator: Takami Mariko 千葉大学, 大学院医学研究院, 助教 (60770906)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: NKT細胞 / 免疫療法 / AhRシグナル / 肺癌

Outline of Final Research Achievements

To improve our current iNKT cell-based immunotherapy for lung cancer, I sought to develop the combination therapy of iNKT cell-based immunotherapy using aryl hydrocarbon receptor (AhR) signaling. I initially focused on the fact that AhR signaling downregulated PD-L1/PD-L2 expression on monocyte-derived dendritic cells and enhanced antitumor activity of iNKT cells. However, the effect of iNKT cell-based immunotherapy was enhanced by adding AhR antagonist instead of AhR agonist in the CT26 s.c. mouse model in vivo. Furthermore, IFN-γ producing cells in CD8+ T cells was increased. These data suggest that the combination of AhR antagonist and iNKT cell-based immunotherapy can be a better treatment option for cancer patients than the current iNKT cell-based immunotherapy.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

我々の研究施設では、NKT細胞を用いた癌免疫療法の臨床応用として、α-GalCerをパルスした樹状細胞投与によりin vivoでNKT細胞を活性化させ抗腫瘍効果を上げる臨床試験を実施し一定の患者における全生存期間の延長が認められるなどの効果を上げてきた。本研究は、肺癌に対するNKT細胞療法の有効性の向上のため新たな併用免疫療法の開発を目的とした。AhRシグナルに着目し、AhRアンタゴニスト投与とNKT細胞療法の併用という新規治療法の可能性を、マウス腫瘍モデルを用いて示唆したことから学術的、社会的に意義のある成果を上げたと考える。