title: T cell responses against tumor associated antigens and prognosis in colorectal cancer patients.
abstract: INTRODUCTION: Spontaneous T cell responses against specific tumor-associated antigens (TAA) are frequently detected in peripheral blood of tumor patients of various histiotypes. However, little is known about whether these circulating, spontaneously occurring, TAA-reactive T cells influence the clinical course of disease. METHODS: Fifty-four HLA-A2 positive colorectal cancer patients had been analyzed for the presence of T cell responses against epitopes derived from the TAA Ep-CAM, her-2/neu, and CEA either by ELISPOT assay or by intracellular cytokine staining. Then, Kaplan-Meier survival analysis was performed comparing T-cell-responders and T-cell-non-responders. For comparison, a group of T-cell-non-responders was compiled stringently matched to T-cell-responders based on clinical criteria and also analyzed for survival. RESULTS: Sixteen out of 54 patients had a detectable T cell response against at least one of the three tested TAA. Two out of 21 patients (9.5%) with limited stage of disease (UICC I and II) and 14 out of 33 patients (42.4%) with advanced disease (UICC III and IV) were T cell response positive. Comparing all T-cell-responders (n = 16) and all T-cell-non-responders (n = 38), no survival difference was found. In an attempt to reduce the influence of confounding clinical factors, we then compared 16 responders and 16 non-responders in a matched group survival analysis; and again no survival difference was found (p = 0.7). CONCLUSION: In summary, we found no evidence that spontaneous peripheral T cell responses against HLA-A2-binding epitopes of CEA, her-2/neu and Ep-CAM are a strong prognostic factor for survival.
authors.affiliation: Medical Department III, Hematology, Oncology, and Transfusion Medicine, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany. dirk.nagorsen@charite.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Nagorsen
authors.forename: Carmen
authors.initials: C
authors.lastname: Scheibenbogen
authors.forename: Anne
authors.initials: A
authors.lastname: Letsch
authors.forename: Christoph-Thomas
authors.initials: CT
authors.lastname: Germer
authors.forename: Heinz-Johannes
authors.initials: HJ
authors.lastname: Buhr
authors.forename: Susanna
authors.initials: S
authors.lastname: Hegewisch-Becker
authors.forename: Licia
authors.initials: L
authors.lastname: Rivoltini
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz