TOWARDS A NETWORK APPROACH IN THE CHARACTERIZATION OF THE IMMUNE RESPONSE IN COLORECTAL CANCER

Abstract

Objectives: Colorectal cancer (CRC) is one of the tumors with a dominant inflammatory component. An impressive volume of research has focused on the potential diagnostic or therapeutic application of the molecules (cytokines, adhesion molecules, others) that alter their expression during inflammation in tumors. However, recently these molecules have been shown to establish complicated relations (cytokine networks) in tumor biology. The present study aims to characterize the cytokine network in colorectal cancer, to highlight the quantitative development of immune modules, the ways in which they are organized and to determine whether there is a superior level coordination in the immune response in colorectal cancer. Methods: The serum levels of nine interleukins (IL-1β, IL-6, IL-8, IL-33, IL-17A, IL-22, IFN (interferon)-γ, IL-4 and IL-10) two cell adhesion molecules-ICAM-1 and P-sel (P-selectin)- and a matrix-metalloproteinase (MMP-7) were measured by ELISA (Enzyme-linked immunosorbent assay) in thirty-three CRC patients and thirty-five healthy controls. Cytokines were selected to represent the main immune networks in CRC. Data were processed in order to find molecules with correlated or group behavior. Results: Three groups or ensembles and a number of independent modules were determined by the present study. Conclusions: The study highlights a heterogenous immune response, with an overall reduced level, with both pro-and antitumoral elements, which tend to be organized into functional groups. This may serve as starting point for strategic approaches in therapy. Keywords: Colorectal, cancer, cytokine, adhesion, network