Analysis of HLA-class II expression and regulation mechanism involved in immune editing of liver cancer microenvironment.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08464
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: University of Fukui
• Principal Investigator: HIRAMATSU KATSUSHI 福井大学, 学術研究院医学系部門(附属病院部), 准教授 (30646849)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肝細胞癌 / HLA-Class II / 腫瘍関連マクロファージ

Outline of Final Research Achievements

Using next-generation sequencing of surgical specimens from 13 hepatocellular carcinoma cases, we identified a group of cases in which HLA-related gene expression was significantly upregulated in cancerous and noncancerous areas. Fluorescence multiplex immunohistochemical staining of tissue samples from 85 hepatocellular carcinoma patients revealed that most of the HLA-DPB1-positive cells in the tumors were CD163-positive M2 macrophages. Furthermore, automated analysis of CD163-positive cell morphology (round, spindle-shaped) using a machine learning algorithm revealed that CD163-positive, round macrophages (round CD163) were significantly increased within tumors (P<0.05) and significantly positively correlated with intratumor CD8 and recurrence-free survival (P<0.05).

Free Research Field

がん腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

肝癌の免疫微小環境において、腫瘍内HLA-DPB1陽性細胞の多くはCD163陽性M２マクロファージであることが判明した。これらは一般的には腫瘍免疫の抑制に関与していると考えられているが、詳細は不明であった。そこで、これらの形態の違い（円形、紡錘形）に注目して検討したところ、CD163陽性・円形マクロファージはCD8陽性リンパ球と共に腫瘍内に存在して無再発生存の延長に寄与していることが明らかとなった。同機序の解明が新たな治療開発につながる可能性が示唆された。