CD4 super(x2b; )CD25 super(x2b; )FOXP3 super(x2b; ) Regulatory T Cells Suppress Anti-Tumor Immune Responses in Patients with Colorectal Cancer

A wealth of evidence obtained using mouse models indicates that CD4 super(x2b; )CD25 super(x2b; )FOXP3 super(x2b; ) regulatory T cells x28; Tregx29; maintain peripheral tolerance to self-antigens and also inhibit anti-tumor immune responses. To date there is limited information about CD4 super(x2b; ) T cell responses in patients with colorectal cancer x28; CRCx29; . We set out to measure T cell responses to a tumor-associated antigen and examine whether Treg impinge on those anti-tumor immune responses in CRC patients. Methodology and Principal Findings Treg were identified and characterized as CD4 super(x2b; )CD25 super(x2b; )FOXP3 super(x2b; ) using flow cytometry. An increased frequency of Treg was demonstrated in both peripheral blood and mesenteric lymph nodes of patients with colorectal cancer x28; CRCx29; compared with either healthy controls or patients with inflammatory bowel disease x28; IBDx29; . Depletion of Treg from peripheral blood mononuclear cells x28; PBMCx29; of CRC patients unmasked CD4 super(x2b; ) T cell responses, as observed by IFN gamma release, to the tumor associated antigen 5T4, whereas no effect was observed in a healthy age-matched control group. Conclusions/Significance Collectively, these data demonstrate that Treg capable of inhibiting tumor associated antigen-specific immune responses are enriched in patients with CRC. These results support a rationale for manipulating Treg to enhance cancer immunotherapy.