Impact of PD-L1/PD-1 crosstalk on cancer cell in pancreatic ductal carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09058
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: Imai Katsunori 熊本大学, 大学院生命科学研究部(医), 特定研究員 (60555746)
• Co-Investigator(Kenkyū-buntansha): 山下 洋市 株式会社麻生(株式会社麻生飯塚病院医学研究推進本部), 外科, 部長 (00404070) ; 岡部 弘尚 熊本大学, 大学院生命科学研究部(医), 特定研究員 (40573621) ; 山尾 宣暢 熊本大学, 大学院生命科学研究部(医), 特定研究員 (70836337)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 膵癌 / 免疫チェックポイント / PD-1 / PD-L1 / 腫瘍免疫

Outline of Final Research Achievements

We investigated the changes of phenotypes including gene and protein expression on pancreatic cancer cell lines by adding recombinant PD-1, however, significant changes were not observed. We thought it could be due to less expression of PD-L1 on pancreatic cancer cell membrane, so we conduct PD-L1 overexpression cells and used in this study. Similarly, however, significant changes were not confirmed between PD-L1 overexpression and Mock cells by adding recombinant PD-L1 protein.
On the other hands, on PD-L1 overexpression cells, EMT-related genes such as Vimentin or Cadherin and cancer stem cell-related genes such as CD133 or CD44 were overexpressed compared to Mock cells. In addition, PD-L1 overexpression cells were significantly associated with cancer drug resistance. Therefore, no we are investigating the details of relationship between PD-L1 expression and EMT, cancer stemness, and cancer drug resistance.

Free Research Field

消化器外科学、肝胆膵外科学、腫瘍免疫学、腫瘍分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は膵癌におけるPD-1/PD-L1の詳細なクロストークを解明することであるが、PD-L1からPD-1へのシグナルではなく、PD-1からPD-L1の逆シグナルを検証し、これが膵癌細胞の増殖や浸潤・転移に与える影響を解明することができれば、難治癌の代表である膵癌治療において、免疫チェックポイント阻害剤の治療成績向上、有用なバイオマーカーの同定、ひいては新たな創薬へと繋がることが期待される。