Significance of CD200 expression and development of novel therapies targeting therapeutic resistance in cholangio and pancreatic cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17660
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Nara Medical University
• Principal Investigator: Nakagawa Kenji 奈良県立医科大学, 医学部附属病院, 研究員 (30812341)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: CD200 / 膵胆道癌 / 癌免疫療法 / 免疫チェックポイント阻害薬

Outline of Final Research Achievements

We investigated the relationship between intratumor expression of candidate molecules such as CD200, CD70, and CD155 and clinicopathological factors and prognosis in resected specimens of cholangio and pancreatic cancer by immunohistochemistry. We analyzed and examined the significance of immune checkpoint expression in the local tumor microenvironmentthe association between the expression of various molecules and intratumor infiltrating immunocompetent cells such as CD4+/CD8+ T cells, CD45RO+ memory T cells, and FOXP-3 in pancreatic cancer and those metastases.
The number of tumor-infiltrating lymphocytes was significantly higher in lung metastases of pancreatic cancer, suggesting activation of anti-tumor immunity. Lung metastases also showed high expression of PD-L1 and TILs, suggesting the efficacy of immune checkpoint inhibitors.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

胆膵癌は他の消化器悪性腫瘍と比較して予後不良であり，新規治療標的分子の同定と，既存の化学療法レジメンの有効活用を図ることが早急に求められている悪性腫瘍の代表である．近年，癌治療における新たな潮流として免疫療法が注目されており，そのターゲットとしてT細胞不活化経路があげられる．免疫回避機構 には複数の分子の関与が示唆されているが，本研究の結果，膵癌肺転移巣では免疫チェックポイント阻害薬等による制御が個別化治療として有効である可能性が示唆された.