Gender-Specific Cytokine Pathways, Targets, and Biomarkers for the Switch from Health to Adenoma and Colorectal Cancer

Studies focusing on gender have shown that differences exist in how the immune system responds to disease and therapy. Understanding how gender influences immunological mechanisms in health and disease and identifying gender-specific biomarkers could lead to specifically tailored treatment and ultimately improve therapeutic success rates. T helper1 (Th1) and Th2 cytokines (Th1/Th2) have pivotal roles in the homeostasis of Th1 and Th2 cell network functions in the immune response but sex steroids affect Th1/Th2 production in different ways and a natural sexual dimorphism in the immune response has been shown. In order to investigate these differences further, we developed Th-cytokine data-driven models of the immune response and evaluated healthy subject peripheral blood samples. Independent cohorts of colorectal cancer and adenoma patients were also studied for comparison purposes. Our results show that the interferon (IFN)γ production pathway for immune response homeostasis is specific to men whilst the interleukin- (IL-) 6 production pathway for immune response homeostasis is specific to women. The IL-10 pathway for restoring immune system resting homeostasis was common to both but was controlled by the respective gender-specific pathways. These gender pathways could well be used as targets and biomarkers in translational research into developing new clinical strategies.