Assessing the prognostic value of preoperative carcinoembryonic antigen-specific T-cell responses in colorectal cancer.

Current dogma suggests that tumor-reactive IFN-γ-producing (TH1-type) T-cells are beneficial to patient outcome; however, the clinical consequence of these responses with respect to long-term prognosis in colorectal cancer (CRC) is not understood. Here, we compared the utility of preoperative, peripheral blood-derived IFN-γ(+) T-cell responses specific to carcinoembryonic antigen (CEA), 5T4, or control antigens (n = 64) with tumor staging and clinical details (n = 87) in predicting five-year outcome of CRC patients who underwent resection with curative intent. Although disease recurrence was more likely in patients with stage III tumors, the presence of preoperative, CEA-specific IFN-γ-producing T-cells identified patients at a statistically significantly greater risk of tumor recurrence following surgical resection, irrespective of tumor stage (odds ratio = 5.00, 95% confidence interval = 1.96 to 12.77, two-sided P <.001). Responses to other antigens, including 5T4, did not reflect outcome. Whilst these results initially appear surprising, they could improve prognostication and help redirect adjuvant treatments.

Review of the pathological results of 2660 appendicectomy specimens.

PURPOSE: Appendicitis is the most commonly performed emergency abdominal surgery. The appendix can also be the site of a variety of neoplasms and unusual inflammatory conditions. A retrospective review was performed to determine the pathological diagnoses in appendicectomy specimens. METHODS: This study is a retrospective analysis of 2660 appendicectomies performed from 1997 to 2003. The reports were analyzed for the following parameters: age-related incidence of acute appendicitis, seasonal variation in presentation, perforation rate, rate of negative and incidental appendicectomy, and the incidence of other pathologies encountered. RESULTS: Of the 2660 appendicectomy specimens, acute appendicitis was seen in 1718 patients (64.58%), with a peak in patients in their second decade (35.09% of cases of acute appendicitis). The perforation rate was 13.9% and was significantly higher in patients aged 70 years or more (P < 0.001). The negative appendicectomy rate was 28.8%, and was significantly higher in female patients (P < 0.001) and in the 11-30 year age group (P < 0.001). Other pathologies include carcinoid (0.52%), adenocarcinoma (0.39%), and mucinous cystadenoma (0.60%). CONCLUSIONS: The high rate of negative appendicectomy among female patients and the increased incidence of perforation in elderly patients reinforce the validity of the judicious use of laparoscopy in these populations. There are still a number of unusual histologies found in appendicectomy specimens supporting the continued use of routine histology.

CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer.

BACKGROUND: A wealth of evidence obtained using mouse models indicates that CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) maintain peripheral tolerance to self-antigens and also inhibit anti-tumor immune responses. To date there is limited information about CD4(+) T cell responses in patients with colorectal cancer (CRC). 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(+)CD25(+)FOXP3(+) using flow cytometry. An increased frequency of Treg was demonstrated in both peripheral blood and mesenteric lymph nodes of patients with colorectal cancer (CRC) compared with either healthy controls or patients with inflammatory bowel disease (IBD). Depletion of Treg from peripheral blood mononuclear cells (PBMC) of CRC patients unmasked CD4(+) T cell responses, as observed by IFNgamma 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.