Scientific publications

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

Nov 15, 2014 | Magazine: Clinical Cancer Research

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), Rizzo M(8), Mazzolini G(8), Pascual JI(9), Andueza MP(2), Perez-Gracia JL(2), Melero I(10).


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.