Microenvironment in hepatocellular carcinoma

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390320
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: SHIRABE Ken 九州大学, 医学(系)研究科(研究院), 准教授 (70264025)
• Co-Investigator(Kenkyū-buntansha): TAKENOYAMA Mitsuhiro 九州がんセンター臨床研究センター, その他部局等, 呼吸器腫瘍科科長 (10309966) ; SOEJIMA Yuji 九州大学, 医学研究院, 共同研究員 (30325526) ; YONEMITSU Yoshikazu 九州大学, 薬学研究院, 教授 (40315065) ; MAEHARA Yoshihiko 九州大学, 医学研究院, 教授 (80165662) ; YOSHIZUMI Tomoharu 九州大学, 大学病院, 講師 (80363373) ; IKEGAMI Toru 九州大学, 大学病院, 助教 (80432938) ; OKANO Shinji 九州大学, 医学研究院, 准教授 (10380429) ; AISHIMA Shinichi 九州大学, 医学研究院, 准教授 (80165662)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肝臓外科学 / PD-L1 / HLA I / 肝細胞癌

Outline of Final Research Achievements

We have shown tumor associated macrophage (TAM) accelerates malignant potential in hepatocellular carcinoma (HCC). Expression of programmed cell death 1 (PD L1) and human leukocyte antigen class I (HLA I) were examined in HCC in the resected specimens. PD-L1 expression was significantly correlated with TAM accumulation and the patients with PD-L1 negative and HLA I positive HCC had favorable prognosis. This suggests that blockade of PD-L1 and PD-1 pathway might be effective therapeutic strategy. In our recent study, PD-L1 expression was significantly correlated with immune suppression and epithelial mesenchymal transition of cancer cells in pancreatic cancer.
To clarify the relationship among IL-17, TAM, PD-1, and PD-L1, subcutaneous tumor model, using IFN sensitive mouse HCC cell line, was established. This model was planned to be applied to IL17KO、and IFN-γKO mouse. Nevertheless, IL17 expression was unstable and we have gotten new KO mouse and we have continued this experiment.

Free Research Field

肝臓外科学