Analysis of Glycan Structures of Immune Checkpoint Molecules and Challenges for Personalized Therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19542
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Showa University
• Principal Investigator: WADA SATOSHI 昭和大学, 大学共同利用機関等の部局等, 教授 (30420102)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 免疫チェックポイント / PD-L1 / 糖鎖構造 / レクチン

Outline of Final Research Achievements

In this study, tumor tissues of each cancer type are used to isolate tumor cells using the laser microdissection (LMD) method, and glycosylation on PD-L1 expressed on tumor cells is analyzed by the high-density lectin array method. First, patient tumor tissues (lung, stomach, colon, and pancreatic cancer) were prepared, and tumor cells of each cancer type were isolated by the LMD method. Next, the isolated tumor cells were immunoprecipitated with anti-PD-L1 antibody to isolate PD-L1 molecules. The isolated PD-L1 molecules were analyzed by high-density lectin array method, and it was found that the lectin structures that recognize carbohydrate chains differ depending on the cancer type. The same results were obtained by high-density lectin array analysis using tumor cell lines.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

糖鎖修飾は種々の生命現象において重要な役割を果たしている。しかしその重要性にも関わらず、遺伝子による直接制御を受けない「翻訳後修飾」であるため研究開発が遅れている。我々は、網羅的かつ定量的な糖鎖解析技術である「高密度レクチンアレイ法」を開発し、生体試料を簡単迅速に解析することを可能とした。本研究成果より、PD-L1上の糖鎖修飾が明らかとなれば、意図的に糖鎖修飾を認識する抗体、更には特定の糖鎖を持つ糖蛋白を標的とした低分子化合物・ペプチド治療薬開発への発展が期待される。将来的には、個々のPD-L1上の糖鎖を標的とした個別化医療へとつながり、学術的・社旗的に大変意義の高い研究と考えられる。