Correlation analysis of receptor binding rate and efficacy or side effects of Immune checkpoint inhibitors of PD-L1

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17033
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Showa University
• Principal Investigator: Hirasawa Yuya 昭和大学, 医学部, 助教 (30834121)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 免疫チェックポイント阻害 / 抗PD-1抗体薬 / 受容体 / 有効性 / 副作用

Outline of Final Research Achievements

Nivolumab, an anti-PD-1 antibody, is usually administered in fixed doses per patient. However, the number of lymphocytes in patients treated with nivolumab is not constant, and there is further variation in the number of P D-1-expressing T cells. Therefore, we decided to clarify the relationship between the efficacy and side effects of anti-PD-1 antibodies and the receptor binding rate. Blood samples were collected from 32 patients with solid tumors treated with nivolumab monotherapy, an anti-PD-1 antibody, before the start of treatment and before the second course of treatment, and the relationship between the PD-1 receptor binding rate (saturation rate) on peripheral blood T cells and efficacy and side effects were analyzed for each T cell fraction. It was suggested that the receptor occupancy rate on regulatory T cells may affect efficacy.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

抗PD-1抗体薬は、T細胞上のPD-1受容体を標的とする。抗PD-1抗体薬を投与された患者のリンパ球数は一定ではなく、PD-1発現T細胞には、CD4陽性、CD８陽性、制御性T細胞を含めさまざまなサブセットから構成され、これらにはそれぞれの活性化のタイミングが違うため、大きなばらつきが存在する。そこで抗PD-1抗体薬の有効性および副作用とT細胞サブセット（分画）における受容体結合率の関連性を明らかにすることがICIsを用いた治療の更なる発展に寄与すると考え本研究を行った。さらに一部のT細胞サブセット上の受容体結合率が有効性に影響することが示唆された。