Research Article Cervical Cancer Cell Supernatants Induce a Phenotypic Switch from U937-Derived Macrophage-Activated M1 State into M2-Like Suppressor Phenotype with Change in Toll-Like Receptor Profile Karina Sánchez-Reyes, 1,2 Alejandro Bravo-Cuellar, 1,3 Georgina Hernández-Flores, 1 José Manuel Lerma-Díaz, 1,3 Luis Felipe Jave-Suárez, 1 Paulina Gómez-Lomelí, 1,2 Ruth de Celis, 1 Adriana Aguilar-Lemarroy, 1 Jorge Ramiro Domínguez-Rodríguez, 1,4 and Pablo Cesar Ortiz-Lazareno 1 1 Divisi´ on de Inmunolog´ ıa, Centro de Investigaci´ on Biom´ edica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, JAL, Mexico 2 Programa de Doctorado en Ciencias Biom´ edicas Orientaci´ on Inmunolog´ ıa, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, 44340 Guadalajara, JAL, Mexico 3 Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitl´ an de Morelos, 47600 Guadalajara, JAL, Mexico 4 Departamento de Farmacobiolog´ ıa, Centro Universitario de Ciencias Exactas e Ingenier´ ıa, Universidad de Guadalajara, 44430 Guadalajara, JAL, Mexico Correspondence should be addressed to Pablo Cesar Ortiz-Lazareno; pablolazareno@gmail.com Received 9 April 2014; Revised 2 September 2014; Accepted 3 September 2014; Published 21 September 2014 Academic Editor: David G. Mutch Copyright © 2014 Karina S´ anchez-Reyes et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cervical cancer (CC) is the second most common cancer among women worldwide. Infection with human papillomavirus (HPV) is the main risk factor for developing CC. Macrophages are important immune efector cells; they can be diferentiated into two phenotypes, identifed as M1 (classically activated) and M2 (alternatively activated). Macrophage polarization exerts profound efects on the Toll-like receptor (TLR) profle. In this study, we evaluated whether the supernatant of human CC cells HeLa, SiHa, and C-33A induces a shif of M1 macrophage toward M2 macrophage in U937-derived macrophages. Results. Te results showed that soluble factors secreted by CC cells induce a change in the immunophenotype of macrophages from macrophage M1 into macrophage M2. U937-derived macrophages M1 released proinfammatory cytokines and nitric oxide; however, when these cells were treated with the supernatant of CC cell lines, we observed a turnover of M1 toward M2. Tese cells increased CD163 and IL-10 expression. Te expression of TLR-3, -7, and -9 is increased when the macrophages were treated with the supernatant of CC cells. Conclusions. Our result strongly suggests that CC cells may, through the secretion of soluble factors, induce a change of immunophenotype M1 into M2 macrophages. 1. Background Cervical cancer (CC) is the second most common cancer among women worldwide [1]. Persistent infection with high- risk human papillomaviruses (HPV), such as HPV-16, - 18, and -45, comprises the most important factors for the development of CC [2–4]. Te frst line of defense against HPV infection in early infection is the innate immune system, which plays a crucial role in viral clearance [5]. Macrophages have long been considered as important immune efector cells involved in primary response to pathogens, normal tissue homeostasis, the presentation of foreign and self-antigens Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 683068, 11 pages http://dx.doi.org/10.1155/2014/683068