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 (Apc^Min/+) 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 Apc^Min/+ mutation on T-cell function, flow cytometric, histochemical, and immunofluorescent studies on both wild-type (Apc^+/+) and Apc^Min/+ mice were performed. We identified decreased levels of interferon gamma (IFN-?⁺)IL-17⁺ double-positive CD4⁺ cells in the mesenteric lymph nodes and Peyer's patches of Apc^Min/+ mice. In addition, altered levels of CD8⁺ cells, and changes in CD8⁺ production of IFN-? and granzyme B were observed. These T-cell alterations did modify tumor immunosurveillance, as the adoptive transfer of splenocytes from Apc^Min/+ animals into a chemically induced CRC model resulted in the inability to prevent epithelial dysplasia. These results suggest an altered T-cell balance in Apc^Min/+ mice may disrupt intestinal homeostasis, consequently limiting intestinal tumor immunosurveillance.

SUBMITTER: Tanner SM 

PROVIDER: S-EPMC5131745 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature