Intestinal microbiota as a predictor of the efficacy of immune checkpoint inhibitors

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K15028
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Fukushima Medical University
• Principal Investigator: Ozaki Yuki 福島県立医科大学, 医学部, 助教 (20791502)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 腸内細菌叢 / 免疫チェックポイント阻害薬 / 効果予測因子

Outline of Final Research Achievements

Stool samples were collected from 25 patients with advanced or recurrent non-small cell lung cancer treated with anti-PD-1 antibody before and after treatment, and 16SrRNA sequencing was performed for intestinal microbiota. We analyzed the α-diversity (intra-group diversity), β-diversity (inter-group diversity), and bacterial species that showed characteristic variation in 25 samples before and 168 samples after treatment. In the analysis of β-diversity of the pre-dose samples, PCoA showed a tendency for the composition of the bacteria in each group to be close. In the analysis of variable bacterial species, several species showed significant variation at the species level in all 168 samples, and Prevotella stercorea was particularly characteristic in the treatment-response group.

Free Research Field

呼吸器外科学

Academic Significance and Societal Importance of the Research Achievements

本研究により抗PD-1抗体による治療を受けた非小細胞肺癌患者において，腸内細菌叢がその効果に何らかの関連がある可能性が示された．しかし，実際の腸内細菌叢の組成と抗PD-1抗体の効果とを直接結びつけることは難しいと考える．更なるステップとして腸内細菌による代謝産物をターゲットとしたメタボロミクス解析が求められるだろう．本研究で得られた抗PD-1抗体の治療反応群で特徴的であった菌種がどのような代謝産物に関わっているのか，またその代謝産物を体内あるいは血中に存在させることで抗PD-1抗体の効果を増強することができる可能性がある．