Elucidation of the mechanism of antitumor immunity enhancing effects of berberine and development of effective combination immunotherapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07758
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: National Cancer Center Japan (2023); Keio University (2019-2020)
• Principal Investigator: Tsukamoto Nobuo 国立研究開発法人国立がん研究センター, 先端医療開発センター, 特任研究員 (20407117)
• Co-Investigator(Kenkyū-buntansha): 河上 裕 国際医療福祉大学, 医学部, 教授 (50161287)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 腫瘍免疫 / がん免疫療法 / berberine

Outline of Final Research Achievements

We identified berberine (BBR), a compound enhancing anti-tumor immunity, and analyzed the mechanism of tumor growth inhibition. BBR administration increased specific phenotypic populations among cancer antigen-specific CD8+ T cells in the draining lymph node and spleen. By contrast, in the tumor microenvironment, BBR administration enhanced cytotoxic activity of cancer antigen-specific CD8+ T cells. The enzymes and cellular states involved in these changes were shown, and the differences in the mechanisms of action in the draining lymph node and spleen and in the tumor were elucidated. We also showed that two mutually inhibitory signals related to the above changes can be activated simultaneously in the same CD8+ T cells. Furthermore, we developed a combination cancer immunotherapy that can synergistically inhibit tumor growth.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

近年、抗CTLA-4抗体や抗PD-1抗体投与、がん抗原特異的T細胞を投与するがん免疫療法の臨床試験においてがん患者の長期生存につながる明確な治療効果が認められているが、それらの奏効率は未だ低く、より効果の高いがん免疫療法の開発が望まれている。本研究の結果は、抗腫瘍免疫増強効果をもつ化合物BBRの作用機序を明らかにした結果、所属リンパ節や脾臓において、また腫瘍において抗腫瘍免疫応答の増強に重要な分子と細胞状態が示された。さらに、腫瘍増殖を相乗的に抑制できる併用がん免疫療法を示すことができ、がん免疫療法、さらには標準治療の改善にもつながると期待される。