PHENOTYPIC AND FUNCTIONAL CHARACTERIZATION OF HUMAN NEUTROPHIL SUBSETS IN PATIENTS WITH COLORECTAL CANCER AND INFLAMMATORY BOWEL DISEASES

Neutrophils play a critical role in the maintenance of intestinal homeostasis while, in pathological conditions, these cells, together with macrophages, T and B lymphocytes, infiltrate the lamina propria where they exert their functions. In murine models of intestinal inflammation and cancer, a change in neutrophils phenotype and its possible functional consequence has already been described while, in humans, there are limited data. Whether mucosal neutrophils play different functional roles in inflammatory bowel diseases (IBD) and colorectal cancer (CRC) is still debated. Here, we report the identification of two populations of human neutrophils (CD15+/CD66bhigh and CD15int/CD66bint) differentially expressed in the peripheral blood and in the gut tissue of IBD and CRC patients. We extensively characterized them phenotipically and we evaluated if the differences observed among groups of patients might correlate with pharmacological treatments; we also evaluated if these circulating and tissue-infiltrating cells also showed a skewing in the functional phenotype towards a more inflammatory or tolerogenic (N1/N2) phenotype. Finally, we evaluated cytokine and ROS production by freshly isolated neutrophils in response to intestinal bacteria.