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

MF Sanmamed, O Carranza-Rua, C Alfaro… - Clinical Cancer …, 2014 - AACR
MF Sanmamed, O Carranza-Rua, C Alfaro, C Onate, S Martín-Algarra, G Perez…
Clinical Cancer Research, 2014AACR
Abstract 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 …
Abstract
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. Clin Cancer Res; 20(22); 5697–707. ©2014 AACR.
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