title: Follicular lymphoma cells induce changes in T-cell gene expression and function: potential impact on survival and risk of transformation.
abstract: OBJECTIVE
  Previous studies have demonstrated the prognostic importance of the immune microenvironment in follicular lymphoma (FL). To investigate the molecular mechanisms during which tumor-infiltrating T cells (TILs) are altered in the FL microenvironment, we studied highly purified CD4 and CD8 TILs from lymph node biopsies at diagnosis in treatment-naive patients with FL compared with reactive tonsils and the peripheral blood of healthy donors.
  
  
  METHODS
  Gene expression profiling of highly purified CD4 and CD8 TILs was performed on the Affymetrix platform. Diagnostic tissue microarrays from an independent patient set (n = 172) were used to verify protein expression and analyze any impact of TIL-expressed genes on outcome. Time-lapse imaging was used to assess T-cell motility.
  
  
  RESULTS
  The most upregulated genes in both CD4 and CD8 TILs were PMCH, ETV1, and TNFRSF9. PMCH is not expressed in peripheral blood T cells, but expression is highly induced on culture with FL. Both CD4 and CD8 TILs from patients with FL have significantly impaired motility compared with those of healthy TILs from reactive tonsils and this can be induced on healthy T cells by FL cells. During multivariate analysis, a model incorporating the number and location of T cells expressing PMCH, NAMPT, and ETV1 showed prognostic significance for overall survival and for time to transformation.
  
  
  CONCLUSIONS
  We showed altered gene expression in TILs in FL and demonstrated that altering the immune microenvironment in FL affects overall survival and time to transformation in this disease.
authors.affiliation: Barts Cancer Institute, The London School of Medicine, Queen Mary, University of London, United Kingdom.
authors.forename: Shahryar
authors.initials: S
authors.lastname: Kiaii
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Clear
authors.forename: Alan G
authors.initials: AG
authors.lastname: Ramsay
authors.forename: Derek
authors.initials: D
authors.lastname: Davies
authors.forename: Ajanthah
authors.initials: A
authors.lastname: Sangaralingam
authors.forename: Abigail
authors.initials: A
authors.lastname: Lee
authors.forename: Maria
authors.initials: M
authors.lastname: Calaminici
authors.forename: Donna S
authors.initials: DS
authors.lastname: Neuberg
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D011979:Receptors, Pituitary Hormone / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012307:Risk Factors; D016019:Survival Analysis; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment / Q000276:immunology; D015854:Up-Regulation
chemical_list: C431280:MCHR2 protein, human; D043562:Receptors, G-Protein-Coupled; D011979:Receptors, Pituitary Hormone