Development of a system for predicting the risk of nivolumab-induced immune-related adverse events

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16400
• 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: Nippon Veterinary and Life Science University (2021-2023); National Cancer Center Japan (2020)
• Principal Investigator: Udagawa Chihiro 日本獣医生命科学大学, 獣医学部, 講師 (20774160)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ファーマコゲノミクス / ゲノムワイド関連解析 / 免疫関連有害事象

Outline of Final Research Achievements

One of the immune checkpoint inhibitors, nivolumab, activates the antitumor cytotoxic activity of T cells. As is common with many cancer treatment strategies, treatment with nivolumab can lead to specific adverse drug reactions, otherwise referred to as immune-related adverse events (irAEs). Although the precise mechanism(s) associated with the development of irAEs remains unclear, it is becoming increasingly important to identify biomarkers to predict the type and possible severity of irAEs that could occur in patients after treatment.
Here, to identify clinically useful genetic markers for predicting the risk of nivolumab-induced irAEs before starting treatment, we performed a genome-wide association study in a total of 622 Japanese patients, and identified 90 SNPs as possible genetic susceptibility factors for the risk of nivolumab-induced irAEs. In the subgroup analysis, we identified an SNP that could be a predictive marker for the risk of nivolumab-induced hypothyroidism.

Free Research Field

ゲノム薬理学

Academic Significance and Societal Importance of the Research Achievements

ニボルマブによるirAEのリスクを評価するための予測マーカーを同定することは、がん患者に安全な治療を提供する上で重要である。本研究は、日本人集団を対象とした初めてのゲノム網羅的な解析であり、関連が示唆されるSNPsを同定した。有意な関連を示すSNPは認められなかったが、本研究成果はさらなる研究に繋がる仮説生成型研究であると考える。今後、追試験や機能的解析が展開されることで、臨床応用可能なマーカーの同定や、irAE発生のメカニズムの解明に貢献することが期待される。