Anti-tumor immune responses mediated by TLR-activated tumor-associated myeloid cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08704
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Nagoya City University (2017-2018); Hokkaido University (2016)
• Principal Investigator: Shime Hiroaki 名古屋市立大学, 大学院医学研究科, 講師 (70372133)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 腫瘍免疫 / がん免疫 / 自然免疫 / TLR / TAM / MDSC / 免疫抑制 / アジュバント

Outline of Final Research Achievements

We analyzed the effects of Toll-like receptor (TLR) 2 or TLR3 signals on myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in tumor-bearing mice. TLR3 activation induced cytotoxic activity of MDSCs against cancer cells, leading to tumor growth inhibition. In combination with radiation treatment, TLR3 ligand-stimulated TAMs enhanced the radiosensitivity of cancer cells to potentiate therapeutic effect. In contrast, TLR2 stimulation enhanced the immunosuppressive activity of MDSCs and TAMs, resulted in decreasing therapeutic efficacy. These results suggest that activation of TLR signaling in MDSCs and TAMs has a significant impact on cancer progression.

Free Research Field

免疫学、腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

がんに対する免疫療法のうち、臨床でも効果が認められている薬剤は、免疫チェックポイント阻害剤に限られる。しかし、全てのがんに有効ではないため、新たな作用機序を持つがん治療薬の開発に向けた基礎研究が必要である。本研究では、腫瘍内の免疫抑制性ミエロイド細胞であるMDSCやTAMの機能制御によるがん治療の可能性を示した。