Analysis of B cell repertoires and their antigen specificity in peripheral blood from cancer patients undergoing anti-PD-1 antibody therapy.

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19490
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Kanagawa Cancer Center Research Institute
• Principal Investigator: Sasada Tetsuro 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), がんワクチン・免疫センター, 部長 (70293967)
• Co-Investigator(Kenkyū-buntansha): 紅露 拓 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), 臨床研究所, 技師・研究員 (90372424)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 抗PD-1抗体 / B細胞 / B細胞受容体レパトア / 抗原 / バイオマーカー / 免疫チェックポイント阻害剤 / 抗腫瘍効果 / 有害事象

Outline of Final Research Achievements

In this study, we have examined the clinical significance of analysis of B cell receptor (BCR) repertoires in peripheral blood from cancer patients undergoing anti-PD-1 antibody therapy. In patients with non-small cell lung cancer (n=30), the diversity of BCR repertoires was significantly reduced in those with better anti-tumor responses. In contrast, in patients with urothelial cancer (n=26), the diversity of BCR repertoires was significantly reduced in those with adverse events. Based on these results, the analysis of BCR repertoires might be clinically useful as a biomarker of immune checkpoint blockade. We are now trying to identify the antigens recognized by BCR from B cells selectively expanded in patients with better anti-tumor responses or adverse events after treatment to elucidate the mechanisms of anti-PD-1 antibody therapy.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果から、BCRレパトア解析のバイオマーカーとしての有用性が示唆された。なお、BCRレパトア多様性の臨床的意義はがん種により異なる可能性があるため、さらに詳細な検討が望まれるが、新たな視点から免疫チェックポイント（PD-1/PD-L1）研究の展開が期待できる。本研究の成果は、抗PD-1抗体の作用メカニズムを解明するとともに、不必要な治療による不利益（有害事象合併・医療費浪費）の回避にもつながる可能性があり、臨床的意義は大きいと思われる。