title: Overexpression of SMARCE1 is associated with CD8+ T-cell infiltration in early stage ovarian cancer.
abstract: T-lymphocyte infiltration in ovarian tumors has been linked to a favorable prognosis, hence, exploring the mechanism of T-cell recruitment in the tumor is warranted. We employed a differential expression analysis to identify genes over-expressed in early stage ovarian cancer samples that contained CD8 infiltrating T-lymphocytes. Among other genes, we discovered that TTF1, a regulator of ribosomal RNA gene expression, and SMARCE1, a factor associated with chromatin remodeling were overexpressed in first stage CD8+ ovarian tumors. TTF1 and SMARCE1 mRNA levels showed a strong correlation with the number of intra-tumoral CD8+ cells in ovarian tumors. Interestingly, forced overexpression of SMARCE1 in SKOV3 ovarian cancer cells resulted in secretion of IL8, MIP1b and RANTES chemokines in the supernatant and triggered chemotaxis of CD8+ lymphocytes in a cell culture assay. The potency of SMARCE1-mediated chemotaxis appeared comparable to that caused by the transfection of the CXCL9 gene, coding for a chemokine known to attract T-cells. Our analysis pinpoints TTF1 and SMARCE1 as genes potentially involved in cancer immunology. Since both TTF1 and SMARCE1 are involved in chromatin remodeling, our results imply an epigenetic regulatory mechanism for T-cell recruitment that invites deciphering.
authors.affiliation: Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, Alexandroupolis, Greece; Division of Genome and Gene Expression Data Analysis, Bioinformatics Institute A*STAR (Agency for Science, Technology and Research), Singapore 138671, Singapore.
authors.forename: Antonis
authors.initials: A
authors.lastname: Giannakakis
authors.affiliation: Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Karapetsas
authors.affiliation: Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, Alexandroupolis, Greece; Department of Oncology, Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.
authors.forename: Denarda
authors.initials: D
authors.lastname: Dangaj
authors.affiliation: Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, Alexandroupolis, Greece; Department of Oncology, Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.
authors.forename: Evripidis
authors.initials: E
authors.lastname: Lanitis
authors.affiliation: Division of Gynecologic Oncology, University of Pennsylvania, Philadelphia, USA.
authors.forename: Janos
authors.initials: J
authors.lastname: Tanyi
authors.affiliation: Department of Oncology, University Hospital of Lausanne (CHUV), Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.
authors.forename: George
authors.initials: G
authors.lastname: Coukos
authors.affiliation: Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, Alexandroupolis, Greece. Electronic address: rmsandal@mbg.duth.gr.
authors.forename: Raphael
authors.initials: R
authors.lastname: Sandaltzopoulos
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D054370:Chemokine CXCL9 / Q000096:biosynthesis; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors
chemical_list: C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C504738:SMARCE1 protein, human; C504003:TTF1 protein, human; D014157:Transcription Factors
keywords: CD8+ T-cell infiltration; CXCL9; Early ovarian cancer; SMARCE1; Termination transcription factor 1