title: Serum interleukin-8 reflects tumor burden and treatment response across malignancies of multiple tissue origins.
abstract: OBJECTIVE
  Interleukin-8 (IL8) is a chemokine produced by malignant cells of multiple cancer types. It exerts various functions in shaping protumoral vascularization and inflammation/immunity. We evaluated sequential levels of serum IL8 in preclinical tumor models and in patients to assess its ability to estimate tumor burden.
  
  
  METHODS
  IL8 levels were monitored by sandwich ELISAs in cultured tumor cells supernatants, tumor-xenografted mice serum, and in samples from 126 patients with cancer. We correlated IL8 serum levels with baseline tumor burden and with treatment-induced changes in tumor burden, as well as with prognosis.
  
  
  RESULTS
  IL8 concentrations correlated with the number of IL8-producing tumor cells in culture. In xenografted neoplasms, IL8 serum levels rapidly dropped after surgical excision, indicating an accurate correlation with tumor burden. In patients with melanoma (n = 16), renal cell carcinoma (RCC; n = 23), non-small cell lung cancer (NSCLC; n = 21), or hepatocellular carcinoma (HCC; n = 30), serum IL8 concentrations correlated with tumor burden and stage, survival (melanoma, n = 16; RCC, n = 23; HCC, n = 33), and objective responses to therapy, including those to BRAF inhibitors (melanoma, n = 16) and immunomodulatory monoclonal antibodies (melanoma, n = 8). IL8 concentrations in urine (n = 18) were mainly elevated in tumors with direct contact with the urinary tract.
  
  
  CONCLUSIONS
  IL8 levels correlate with tumor burden in preclinical models and in patients with cancer. IL8 is a potentially useful biomarker to monitor changes in tumor burden following anticancer therapy, and has prognostic significance.
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain. Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain.
authors.forename: Miguel F
authors.initials: MF
authors.lastname: Sanmamed
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Omar
authors.initials: O
authors.lastname: Carranza-Rua
authors.affiliation: Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Alfaro
authors.affiliation: Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Oñate
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Martín-Algarra
authors.affiliation: Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain.
authors.forename: Guiomar
authors.initials: G
authors.lastname: Perez
authors.affiliation: Department of Biochemistry, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Sara F
authors.initials: SF
authors.lastname: Landazuri
authors.affiliation: Department of Biochemistry, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Gonzalez
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Gross
authors.affiliation: Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Rodriguez
authors.affiliation: Department of Immunology, Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Muñoz-Calleja
authors.affiliation: Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Rodríguez-Ruiz
authors.affiliation: Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Pamplona, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sangro
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: López-Picazo
authors.affiliation: Gene Therapy Laboratory, Department of Medicine, Facultad de Ciencias Biomédicas, Universidad Austral, Pilar, Argentina.
authors.forename: Manglio
authors.initials: M
authors.lastname: Rizzo
authors.affiliation: Gene Therapy Laboratory, Department of Medicine, Facultad de Ciencias Biomédicas, Universidad Austral, Pilar, Argentina.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mazzolini
authors.affiliation: Department of Urology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Pascual
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Andueza
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Perez-Gracia
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain. Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain. imelero@unav.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D016209:Interleukin-8 / Q000097:blood*; D018345:Mice, Knockout; D009369:Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D016209:Interleukin-8