Analysis of tumor immunomodulatory mechanisms in the microenvironment of highly metastatic, highly invasive oral cancer.

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K17221
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Kanazawa University
• Principal Investigator: hirai mariko 金沢大学, 医学系, 協力研究員 (40802830)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: PD-L1

Outline of Final Research Achievements

Based on the following four study items, this study investigated MMPs that are reduced in EMT-induced formation of 4D type highly invasive oral cancer cells and cancer-associated fibroblasts. In addition, MMP which degrades PD-L1 was identified, and among the existing anticancer drugs, those which elevate this MMPs expression were identified. 1, Identification of MMPs that are reduced during EMT-induced formation of type 4D highly invasive oral cancers and cancer-associated fibroblasts. 2, Examination of PD-L1 degradation activity of MMPs, which are decreased in 4D type highly invasive oral cancer and cancer-associated fibroblasts by inducing EMTs. 3, Examination of the cleavage activity of PD-L1 by MMPs. 4, Investigation of anticancer drugs that increase the expression of MMPs with degradative activity of PD-L1.

Free Research Field

口腔癌

Academic Significance and Societal Importance of the Research Achievements

本研究結果は、PD-1とPD-1リガンドが発見されるまで詳細な解析対象とされてこなかった4D型口腔癌微小環境での免疫寛容に焦点をあて、MMPによる腫瘍免疫調節が高転移性高浸潤型口腔癌へと誘導する可能性を検証した点で独創的である。また、PD-L1の分解を通して腫瘍免疫活性化に働くMMP発現を上昇させる抗がん剤は、抗PD-1療法と併用して効果を高める可能性も考えられる。本研究から得られる結果は、近年急速に注目されている癌免疫療法の有効性を高めるための有益な情報を与える点で意義がある。