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.

Figure 1

Kaplan-Meier survival analyses of colorectal cancer patients based on their T cell response state. Dashed lines refer to T-cell-responders, full lines refer to T-cell-non-responders, crosses mark censored cases. Time point 0 refers to the time of blood draw for T cell analysis. A. Two groups of CRC patients (total n = 54) were analyzed for survival after T cell analysis. One group had a spontaneous T cell response against the tumor associated antigens CEA, Ep-CAM, or her-2/neu (n = 16, dashed line). The other group had no T cell response against these antigens (n = 38, full line). No survival difference between the groups was found (log rank, p = 0.4). B. Two matched groups of CRC patients (total n = 32) were analyzed for survival after T cell analysis. One group had a spontaneous T cell response against tumor antigens CEA, Ep-CAM, or her-2/neu (n = 16, dashed line). The other group had no T cell response against these antigens and was selected by having similar clinical characteristics for stage, gender, presence of clinically detectable tumor at time of blood draw, duration of disease, age, and prior therapy (n = 16, full line). No survival difference was found (log rank, p = 0.7).