title: Assessing the prognostic value of preoperative carcinoembryonic antigen-specific T-cell responses in colorectal cancer.
abstract: 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.
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK (MJS, CMB, DFCB, AwG, AnG); Nuffield Department of Surgical Sciences, Oxford University, John Radcliffe Hospital, Oxford, UK (GJB); Department of Colorectal Surgery, University Hospital of Wales, Cardiff, UK (BIR); Cancer Trials Unit (Translational Statistics), School of Medicine, Cardiff University, Cardiff, UK (RKH); Department of Integrated Medicine, University Hospital of Wales, Cardiff, UK (AnG).
authors: Martin J
authors: MJ
authors: Scurr
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK (MJS, CMB, DFCB, AwG, AnG); Nuffield Department of Surgical Sciences, Oxford University, John Radcliffe Hospital, Oxford, UK (GJB); Department of Colorectal Surgery, University Hospital of Wales, Cardiff, UK (BIR); Cancer Trials Unit (Translational Statistics), School of Medicine, Cardiff University, Cardiff, UK (RKH); Department of Integrated Medicine, University Hospital of Wales, Cardiff, UK (AnG).
authors: Clare M
authors: CM
authors: Brown
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK (MJS, CMB, DFCB, AwG, AnG); Nuffield Department of Surgical Sciences, Oxford University, John Radcliffe Hospital, Oxford, UK (GJB); Department of Colorectal Surgery, University Hospital of Wales, Cardiff, UK (BIR); Cancer Trials Unit (Translational Statistics), School of Medicine, Cardiff University, Cardiff, UK (RKH); Department of Integrated Medicine, University Hospital of Wales, Cardiff, UK (AnG).
authors: Diana F
authors: DF
authors: Costa Bento
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK (MJS, CMB, DFCB, AwG, AnG); Nuffield Department of Surgical Sciences, Oxford University, John Radcliffe Hospital, Oxford, UK (GJB); Department of Colorectal Surgery, University Hospital of Wales, Cardiff, UK (BIR); Cancer Trials Unit (Translational Statistics), School of Medicine, Cardiff University, Cardiff, UK (RKH); Department of Integrated Medicine, University Hospital of Wales, Cardiff, UK (AnG).
authors: Gareth J
authors: GJ
authors: Betts
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK (MJS, CMB, DFCB, AwG, AnG); Nuffield Department of Surgical Sciences, Oxford University, John Radcliffe Hospital, Oxford, UK (GJB); Department of Colorectal Surgery, University Hospital of Wales, Cardiff, UK (BIR); Cancer Trials Unit (Translational Statistics), School of Medicine, Cardiff University, Cardiff, UK (RKH); Department of Integrated Medicine, University Hospital of Wales, Cardiff, UK (AnG).
authors: Brian I
authors: BI
authors: Rees
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK (MJS, CMB, DFCB, AwG, AnG); Nuffield Department of Surgical Sciences, Oxford University, John Radcliffe Hospital, Oxford, UK (GJB); Department of Colorectal Surgery, University Hospital of Wales, Cardiff, UK (BIR); Cancer Trials Unit (Translational Statistics), School of Medicine, Cardiff University, Cardiff, UK (RKH); Department of Integrated Medicine, University Hospital of Wales, Cardiff, UK (AnG).
authors: Robert K
authors: RK
authors: Hills
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK (MJS, CMB, DFCB, AwG, AnG); Nuffield Department of Surgical Sciences, Oxford University, John Radcliffe Hospital, Oxford, UK (GJB); Department of Colorectal Surgery, University Hospital of Wales, Cardiff, UK (BIR); Cancer Trials Unit (Translational Statistics), School of Medicine, Cardiff University, Cardiff, UK (RKH); Department of Integrated Medicine, University Hospital of Wales, Cardiff, UK (AnG).
authors: Awen
authors: A
authors: Gallimore
authors: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK (MJS, CMB, DFCB, AwG, AnG); Nuffield Department of Surgical Sciences, Oxford University, John Radcliffe Hospital, Oxford, UK (GJB); Department of Colorectal Surgery, University Hospital of Wales, Cardiff, UK (BIR); Cancer Trials Unit (Translational Statistics), School of Medicine, Cardiff University, Cardiff, UK (RKH); Department of Integrated Medicine, University Hospital of Wales, Cardiff, UK (AnG).
authors: Andrew
authors: A
authors: Godkin
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology*; D009367:Neoplasm Staging; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D008562:Membrane Glycoproteins; C063709:trophoblastic glycoprotein 5T4, human; D007371:Interferon-gamma