title: Inflammatory and regulatory T cells contribute to a unique immune microenvironment in tumor tissue of colorectal cancer patients.
abstract: Colorectal cancer is one of the five leading causes of cancer mortality worldwide. The mechanisms of pathogen clearance, inflammation and regulation by T cells in the healthy bowel are also important in controlling tumor growth. The majority of studies analyzing T cells and their relationship to colorectal tumor growth have focused on individual T cell markers or gene clusters and thus the complexity of the T cell response contributing to the growth of the tumor is not clear. We have studied the T cells in colorectal cancer patients and have defined a unique T cell signature for colorectal tumor tissue. Using a novel analytical flow cytometric approach in concert with confocal microscopy, we have shown that the tumor has a lower frequency of effector T cells (CD69+), but a higher frequency of both regulatory (CD25hi Foxp3+) and inflammatory T cells (IL-17+) compared with associated nontransformed bowel tissue. We have also identified minor populations of T cells expressing conventional markers of both inflammatory and regulatory T cells (CD4+IL-17+Foxp3+) in the tumor tissue. These cells may represent intermediate populations or they may dictate an inflammatory versus regulatory function in surrounding T cells. Together, these data describe an immune microenvironment in colorectal cancer unique to the tumor tissue and distinct from the surrounding healthy bowel tissue, and this distinct environment is reflected by a gradient of T cells expressing markers of multiple T cell populations. These findings may be used to improve diagnosis and prognosis of colorectal cancer patients.
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
authors.forename: Adam
authors.initials: A
authors.lastname: Girardin
authors.forename: John
authors.initials: J
authors.lastname: McCall
authors.forename: Michael A
authors.initials: MA
authors.lastname: Black
authors.forename: Francesca
authors.initials: F
authors.lastname: Edwards
authors.forename: Vicky
authors.initials: V
authors.lastname: Phillips
authors.forename: Edward S
authors.initials: ES
authors.lastname: Taylor
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Reeve
authors.forename: Roslyn A
authors.initials: RA
authors.lastname: Kemp
mesh_terms: D015179:Colorectal Neoplasms / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D018613:Microscopy, Confocal; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D059016:Tumor Microenvironment
chemical_list: D020381:Interleukin-17