Gene Expression and Pathway Analysis of Quiescent CD8+ T Cells from Liver Cancer, Liver Sinusoid and Peripheral Blood - Study on Toxicogenomics and Prevention Targeting

The quiescent status of T cell immunology is associated with the development of tumor in liver cancer. However, the cause of T cell quiescence in the tumor microenvironment is still unclear. Recently, it has been proposed that toxic substances could inhibit T-cell immune response to tumor cells. Since sinusoidal structure is primarily involved in anti-toxic function and toxic retaining mechanism, in this paper we study the role of liver sinusoid in liver tumor by comparing gene expression levels of quiescent genes in CD8+ T cells isolated from three sources: peripheral blood, sinusoidal structure, and tumor tissue. We observed that most quiescent genes are up regulated in CD8+ T cells isolated from sinusoidal structure as compared with those from liver tumor and peripheral blood. The genes and pathways predicted in this project will be candidates for drug targeting.

[1]  Filip Braet,et al.  Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: a review , 2002, Comparative hepatology.

[2]  D. Fruman,et al.  Regulation of quiescence in lymphocytes. , 2003, Trends in immunology.

[3]  Wei Zhang,et al.  Genomic expression analysis by single‐cell mRNA differential display of quiescent CD8 T cells from tumour‐infiltrating lymphocytes obtained from in vivo liver tumours , 2009, Immunology.

[4]  Anne F. Buckley,et al.  Transcription factor LKLF is sufficient to program T cell quiescence via a c-Myc–dependent pathway , 2001, Nature Immunology.

[5]  Biaoru Li,et al.  Identification of mRNAs expressed in tumor-infiltrating lymphocytes by a strategy for rapid and high throughput screening. , 2000, Gene.

[6]  A. Rice,et al.  Identification of LKLF-regulated genes in quiescent CD4+ T lymphocytes. , 2005, Molecular immunology.

[7]  Mark Connors,et al.  Quiescent phenotype of tumor-specific CD8+ T cells following immunization. , 2004, Blood.

[8]  Naoto Hirano,et al.  Tob is a negative regulator of activation that is expressed in anergic and quiescent T cells , 2001, Nature Immunology.

[9]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  David Zhang,et al.  The crosstalk between EGF, IGF, and Insulin cell signaling pathways - computational and experimental analysis , 2009, BMC Systems Biology.

[11]  C. Li,et al.  Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Peter Neuhaus,et al.  Immune reactivity is more suppressed in patients with alcoholic liver disease than in patients with virus-induced cirrhosis after CRH stimulation. , 2006, Alcoholism, clinical and experimental research.

[13]  Rabih Bechara,et al.  Cytokines and alcohol. , 2006, Alcoholism, clinical and experimental research.

[14]  William L Redmond,et al.  Peripheral tolerance of CD8 T lymphocytes. , 2005, Immunity.

[15]  Fernando A Arosa,et al.  CD8+CD28– T cells: Certainties and uncertainties of a prevalent human T‐cell subset , 2002, Immunology and cell biology.

[16]  D. Adams,et al.  Recruitment of lymphocytes to the human liver , 2002, Immunology and cell biology.

[17]  Biaoru Li,et al.  Tumor tissue recycling--a new combination treatment for solid tumors: experimental and preliminary clinical research. , 1999, In vivo.

[18]  K. J. Dean,et al.  Mercury Impairment of Mouse Thymocyte Survival in Vitro: Involvement of Cellular Thiols , 2005, Journal of toxicology and environmental health. Part A.

[19]  S. M. Barker,et al.  Histochemical analysis of liver cells from short term, aflatoxin-dosed and nondosed Coturnix coturnix japonica. 1. Aflatoxin-sensitive quail. , 1983, Poultry science.

[20]  David Zhang,et al.  SimBoolNet—a Cytoscape plugin for dynamic simulation of signaling networks , 2009, Bioinform..