C-J Lei1, B Wang, Z-X Long, H Ren, Q-Y Pan, Y Li. 1. Department of Tumor Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xian, Shanxi, China. hongreneij@sohu.com.
Abstract
OBJECTIVE: Immune therapy has recently become a novel strategy for treating liver cancer, making it of critical importance to identify novel targets for treatment. Programmed death-1 homology (PD-1H) is one newly discovered negative co-stimulating molecule, and plays important regulatory roles in suppressing T cell activation. However, the expression or function of PD-1H in liver tumors has not been reported. MATERIALS AND METHODS: Liver cancer tissues were collected from The Cancer Genome Atlas (TCGA) (http://tcga-data.nci-nih.gov). This study then utilized diethylnitrosamine (DEN) induced liver cancer mice, on which PD-1H monoclonal antibody and PD-1H extra-cellular Fc domain fusion protein were injected intraperitoneal. General status, gross morphology of liver tissues was examined, followed by hematoxylin-eosin (HE) staining and plotting survival curve. RESULTS: Among TCGA samples, PD-1H expression was significantly elevated. Induced liver cancer mice showed depressed mental status, early onset of hepatitis and liver cirrhosis. Five mice dead in model group (mortality=33.33%). No natural death occurred in control group. Injection of PD-1H-Fc-Ig fusion and PD-1H monoclonal antibody improved the condition to certain extents, with morality at about 20%. Comparing to DEN group, combined treatment group showed significantly fewer tumor lesion on liver surface, with increased body weight and lower liver-body weight ratio. HE staining showed significantly elevated ratio of normal cells in combined treatment group, although large amounts of cancer cells still existed. CONCLUSIONS: Blocking of PD-1H signal pathway could suppress liver cancer cell growth, decrease mouse mortality, indicating promising application of PD-1H in tumor immune therapy.
OBJECTIVE: Immune therapy has recently become a novel strategy for treating liver cancer, making it of critical importance to identify novel targets for treatment. Programmed death-1 homology (PD-1H) is one newly discovered negative co-stimulating molecule, and plays important regulatory roles in suppressing T cell activation. However, the expression or function of PD-1H in liver tumors has not been reported. MATERIALS AND METHODS:Liver cancer tissues were collected from The Cancer Genome Atlas (TCGA) (http://tcga-data.nci-nih.gov). This study then utilized diethylnitrosamine (DEN) induced liver cancermice, on which PD-1H monoclonal antibody and PD-1H extra-cellular Fc domain fusion protein were injected intraperitoneal. General status, gross morphology of liver tissues was examined, followed by hematoxylin-eosin (HE) staining and plotting survival curve. RESULTS: Among TCGA samples, PD-1H expression was significantly elevated. Induced liver cancermice showed depressed mental status, early onset of hepatitis and liver cirrhosis. Five mice dead in model group (mortality=33.33%). No natural death occurred in control group. Injection of PD-1H-Fc-Ig fusion and PD-1H monoclonal antibody improved the condition to certain extents, with morality at about 20%. Comparing to DEN group, combined treatment group showed significantly fewer tumor lesion on liver surface, with increased body weight and lower liver-body weight ratio. HE staining showed significantly elevated ratio of normal cells in combined treatment group, although large amounts of cancer cells still existed. CONCLUSIONS: Blocking of PD-1H signal pathway could suppress liver cancer cell growth, decrease mousemortality, indicating promising application of PD-1H in tumor immune therapy.