title: Circulating levels of TNF receptor II are prognostic for patients with peripheral T-cell non-Hodgkin lymphoma.
abstract: OBJECTIVE
  Peripheral T-cell non-Hodgkin lymphomas (T-NHL) represent a small but heterogeneous and clinically aggressive subset of NHLs with a poor outcome. Cytokines or their receptors might be associated with the clinical outcome of these lymphomas. Therefore, we tested whether gene variations and serum levels of soluble TNF receptor (TNFR)I (sTNFRI), sTNFRII, interleukin (IL)-10, or sIL-4R are predictive for treatment response in T-NHLs.
  
  
  METHODS
  Peripheral blood DNA from 117 patients with T-NHL treated in prospective clinical trials was subjected to genotyping analysis. Whenever possible, pretreatment sera were obtained, and circulating levels of sTNFRI, sTNFRII, IL-10, and sIL-4R were determined with a specific capture enzyme-linked immunoassay.
  
  
  RESULTS
  Patients characterized by TNFRI-609GG (rs4149570) showed a trend toward better event free survival [EFS; univariate: P = 0.041; multivariate: HR, 1.76; confidence interval (CI), 0.99-3.14 with P = 0.056]. A protective role of IL-10-1087A, -824T, and -597A reported in another study was not confirmed in our cohort. Patients with circulating levels of soluble TNFRII ≥2.16 ng/mL had a 2.07-fold increased relative risk for shorter overall survival (OS; univariate: P = 0.0034; multivariate: HR, 2.07; CI, 0.92-4.70 with P = 0.081) and a 2.49-fold higher risk for shorter EFS (univariate: P = 0.00068; multivariate: HR, 2.49; CI, 1.22-5.08 with P = 0.012). Elevations of circulating levels of sTNFRI, IL-10, and sIL-4R are frequent, but the clinical response in these patients is not significantly different.
  
  
  CONCLUSIONS
  Our findings suggest a critical role for TNF-TNFR signaling for the clinical outcome of patients with peripheral T-NHLs.
authors.affiliation: Department of Hematology and Oncology, Medical Center of the Georg-August-University Göttingen, Germany. christina.heemann@med.uni-goettingen.de
authors.forename: Christina
authors.initials: C
authors.lastname: Heemann
authors.forename: Markus
authors.initials: M
authors.lastname: Kreuz
authors.forename: Irene
authors.initials: I
authors.lastname: Stoller
authors.forename: Nils
authors.initials: N
authors.lastname: Schoof
authors.forename: Frederike
authors.initials: F
authors.lastname: von Bonin
authors.forename: Marita
authors.initials: M
authors.lastname: Ziepert
authors.forename: Markus
authors.initials: M
authors.lastname: Löffler
authors.forename: Wolfram
authors.initials: W
authors.lastname: Jung
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.forename: Dieter
authors.initials: D
authors.lastname: Kube
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D053208:Kaplan-Meier Estimate; D016411:Lymphoma, T-Cell, Peripheral / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood* / Q000235:genetics; D012306:Risk; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C508609:IL10 protein, human; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D016753:Interleukin-10