Elucidation of molecular mechanism of CpG-mediated suppression of malignant progression of tumors via activated T cell-released exosomes

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16411
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Mie University
• Principal Investigator: Momose Fumiyasu 三重大学, 医学系研究科, 産学官連携講座助教 (20798326)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CpG / がん悪性化制御 / T細胞 / エクソソーム / マクロファージ

Outline of Final Research Achievements

In this study, intratumoral administration of CpG showed anti-tumor effects not only on CpG-administered local tumors, but also on distant tumors at non-administered sites.
We found that CpG improved the tumor microenvironment which promotes tumor invasion and metastasis, acts on anti-tumor immunosuppression, such as tumor stroma and tumor-associated macrophages, and suppressed malignant progression of tumors. In addition, CpG promoted the production of exosomes and above effects of CpG were inhibited by administration of exosome inhibitors. These results suggest exosomes were involved in systemic effects of CpG. Furthermore, the exploratory study of combination therapy of CpG and cancer immunotherapy showed the treatment of CpG with cancer vaccines and T cell therapy could exhibit more effective anti-tumor effects.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

遠隔転移を伴うがんの生存率は、早期原発がんと比較して著しく低下する。そのため、現在がんの浸潤や転移を標的とした治療薬の早急な研究開発が社会的に求められている。本研究では、CpGの腫瘍内投与が、腫瘍の浸潤や転移等のがんの悪性化を促すがん間質組織や腫瘍関連マクロファージ等の腫瘍微小環境中の抗腫瘍免疫抑制環境を抑制することを明らかにし、エクソソームの産生を介して全身性の抗腫瘍効果を誘導する可能性を示した。本研究を基礎とした今後の進展によりさらに本機構について解明できれば、がん浸潤・転移阻害薬の創製やCpGと免疫療法を併用した複合的がん免疫療法の開発が期待できる。