Exploreatory research of drug resistance mechanisms based on exosome information in the cancer microenvironment

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09043
• 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: Wakayama Medical University
• Principal Investigator: Ueno Masaki 和歌山県立医科大学, 医学部, 准教授 (90405465)
• Co-Investigator(Kenkyū-buntansha): 速水 晋也 和歌山県立医科大学, 医学部, 講師 (00468290) ; 山上 裕機 和歌山県立医科大学, 医学部, 学長特命教員(特別顧問) (20191190) ; 川井 学 和歌山県立医科大学, 医学部, 教授 (40398459)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 肝細胞癌 / 免疫チェックポイント阻害剤 / 癌微小環境

Outline of Final Research Achievements

In the microenvironment of hepatocellular carcinoma, the relationship between the expression of various proteins in tumors and the expression of immune system cytokines was analyzed, and it some subclass classification was confirmed that there were some tumor clusters with strong immunogenicity. Meanwhile, in clinical cases performing atezolizumab and bevacizumab, the effectiveness of the treatment could be predicted from tumor characteristics and serum parameters. Alpha-fetoprotein (AFP), C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) were extracted as significant predictive factors. The factors reflecting the host condition, such as CRP and NLR, as well as the malignancy of the tumor itself, also affected the effectiveness of these drug therapies.

Free Research Field

肝臓外科

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌の癌微小環境において、多様な遺伝変異と相関して、腫瘍の免疫原性も多様であり、周辺の免疫担当細胞の分布も多様であることが分かった。免疫チェックポイント阻害剤を用いた治療を行う際は、このような腫瘍自体の多様性と免疫原性の程度を評価するとともに、患者自身の抗腫瘍免疫状態も効果に影響を及ぼすことが分かり、宿主側の環境因子も今後調査する必要性があることが分かった。