title: Altered T-Cell Balance in Lymphoid Organs of a Mouse Model of Colorectal Cancer.
abstract: The adenomatous polyposis coli (APC) gene is a known tumor suppressor gene, and mice with mutations in Apc (ApcMin/+) spontaneously form multiple intestinal neoplasms. In this model of human colorectal cancer (CRC), it has been reported that CD4+T-cell-derived interleukin 17 (IL-17) promotes intestinal tumor development, but it is not known if the Apc mutation actually directly alters T-cell function and subsequently tumor immunosurveillance. To investigate the ApcMin/+mutation on T-cell function, flow cytometric, histochemical, and immunofluorescent studies on both wild-type (Apc+/+) and ApcMin/+mice were performed. We identified decreased levels of interferon gamma (IFN-γ+)IL-17+double-positive CD4+cells in the mesenteric lymph nodes and Peyer's patches of ApcMin/+mice. In addition, altered levels of CD8+cells, and changes in CD8+production of IFN-γ and granzyme B were observed. These T-cell alterations did modify tumor immunosurveillance, as the adoptive transfer of splenocytes from ApcMin/+animals into a chemically induced CRC model resulted in the inability to prevent epithelial dysplasia. These results suggest an altered T-cell balance in ApcMin/+mice may disrupt intestinal homeostasis, consequently limiting intestinal tumor immunosurveillance.
authors: Department of Biological, Physical, and Earth Sciences, Limestone College, Gaffney, South Carolina (SMT).|Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (CAM)
authors: Scott M
authors: SM
authors: Tanner
authors: Department of Natural Sciences and Mathematics, Lee University, Cleveland, Tennessee (JGD).
authors: Joseph G
authors: JG
authors: Daft
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama (SAH, RGL)
authors: Stephanie A
authors: SA
authors: Hill
authors: Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (CAM)
authors: Colin A
authors: CA
authors: Martin
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama (SAH, RGL)
authors: Robin G
authors: RG
authors: Lorenz
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016764:Cell Polarity; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D053804:Granzymes / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008643:Mesentery / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D010581:Peyer's Patches / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D020381:Interleukin-17; D007371:Interferon-gamma; D053804:Granzymes
keywords: CD4; CD8; T cell; colorectal cancer; interferon gamma; interleukin 17; mouse model; mucosal immunity; tumor immunosurveillance