Serum Interleukin-8 Reflects Tumor Burden and Treatment Response across Malignancies of Multiple Tissue Origins

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 levelsweremonitored by sandwich ELISAs incultured tumor cells supernatants, tumor-xenograftedmice serum, and in samples from126 patients with cancer. Wecorrelated IL8 serumlevels 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. Fil: Sanmamed, Miguel F.. Universidad de Navarra; España Fil: Carranza Rua, Omar. Universidad de Navarra; España Fil: Alfaro, Carlos. Universidad de Navarra; España Fil: Oñate, Carmen. Universidad de Navarra; España Fil: Martín Algarra, Salvador. Universidad de Navarra; España Fil: Perez, Guiomar. Universidad de Navarra; España Fil: Landazuri, Sara F.. Universidad de Navarra; España Fil: Gonzalez, Alvaro. Universidad de Navarra; España Fil: Gross, Stefanie. University Hospital Erlangen; Alemania Fil: Rodriguez, Inmaculada. Universidad de Navarra; España Fil: Muñoz Calleja, Cecilia. Universidad Autonoma de Madrid. Hospital Universitario de la Princesa; España Fil: Rodríguez Ruiz, María. Universidad de Navarra; España Fil: Sangro, Bruno. Universidad de Navarra; España Fil: López Picazo, José M.. Universidad de Navarra; España Fil: Rizzo, Manglio Miguel. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Pascual, Juan I.. Universidad de Navarra; España Fil: Andueza, Maria Pilar. Universidad de Navarra; España Fil: Perez Gracia, Jose Luis. Universidad de Navarra; España Fil: Melero, Ignacio. Universidad de Navarra; España