Scientific publications

Serum interleukin-8 reflects tumor burden and treatment response across malignancies of multiple tissue origins

Sanmamed MF(1), Carranza-Rua O(2), Alfaro C(3), Oñate C(3), Martín-Algarra S(2), Perez G(3), Landazuri SF(4), Gonzalez A(4), Gross S(5), Rodriguez I(3), Muñoz-Calleja C(6), Rodríguez-Ruiz M(3), Sangro B(7), López-Picazo JM(2) [SP], Rizzo M(8), Mazzolini G(8), Pascual JI(9), Andueza MP(2), Perez-Gracia JL(2) [SP], Melero I(10) [SP].

(1) Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain. Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain.
(2) Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
(3) Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain.
(4) Department of Biochemistry, Clínica Universidad de Navarra, Pamplona, Spain.
(5) Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
(6) Department of Immunology, Hospital Universitario de la Princesa, Madrid, Spain.
(7) Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Pamplona, Spain.
(8) Gene Therapy Laboratory, Department of Medicine, Facultad de Ciencias Biomédicas, Universidad Austral, Pilar, Argentina.
(9) Department of Urology, Clínica Universidad de Navarra, Pamplona, Spain.
(10) Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain. Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain.

Magazine: Clinical Cancer Research

Date: Nov 15, 2014

Medical Oncology Internal Medicine [SP] Urology [SP]

PURPOSE:
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.

EXPERIMENTAL DESIGN:
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.

CITATION  Clin Cancer Res. 2014 Nov 15;20(22):5697-707. doi: 10.1158/1078-0432.CCR-13-3203.

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