T cell responses against tumor associated antigens and prognosis in colorectal cancer patients

Dirk Nagorsen, Carmen Scheibenbogen, Anne Letsch, Christoph Thomas Germer, Heinz Johannes Buhr, Susanna Hegewisch-Bcker, Licia Rivoltini, Eckhard Thiel, Ulrich Keilholz

Research output: Contribution to journalArticle

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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.

Original languageEnglish
JournalJournal of Translational Medicine
Volume3
DOIs
Publication statusPublished - Jan 19 2005

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T-cells
Neoplasm Antigens
Tumors
Colorectal Neoplasms
T-Lymphocytes
Antigens
HLA-A2 Antigen
Survival
Computer aided manufacturing
Survival Analysis
Epitopes
Enzyme-Linked Immunospot Assay
Kaplan-Meier Estimate
Assays
Blood
Research Design

Keywords

  • Antigen
  • Colorectal cancer
  • Prognosis
  • Survival
  • T cell response

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Nagorsen, D., Scheibenbogen, C., Letsch, A., Germer, C. T., Buhr, H. J., Hegewisch-Bcker, S., ... Keilholz, U. (2005). T cell responses against tumor associated antigens and prognosis in colorectal cancer patients. Journal of Translational Medicine, 3. https://doi.org/10.1186/1479-5876-3-3

T cell responses against tumor associated antigens and prognosis in colorectal cancer patients. / Nagorsen, Dirk; Scheibenbogen, Carmen; Letsch, Anne; Germer, Christoph Thomas; Buhr, Heinz Johannes; Hegewisch-Bcker, Susanna; Rivoltini, Licia; Thiel, Eckhard; Keilholz, Ulrich.

In: Journal of Translational Medicine, Vol. 3, 19.01.2005.

Research output: Contribution to journalArticle

Nagorsen, D, Scheibenbogen, C, Letsch, A, Germer, CT, Buhr, HJ, Hegewisch-Bcker, S, Rivoltini, L, Thiel, E & Keilholz, U 2005, 'T cell responses against tumor associated antigens and prognosis in colorectal cancer patients', Journal of Translational Medicine, vol. 3. https://doi.org/10.1186/1479-5876-3-3
Nagorsen, Dirk ; Scheibenbogen, Carmen ; Letsch, Anne ; Germer, Christoph Thomas ; Buhr, Heinz Johannes ; Hegewisch-Bcker, Susanna ; Rivoltini, Licia ; Thiel, Eckhard ; Keilholz, Ulrich. / T cell responses against tumor associated antigens and prognosis in colorectal cancer patients. In: Journal of Translational Medicine. 2005 ; Vol. 3.
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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.",
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AU - Germer, Christoph Thomas

AU - Buhr, Heinz Johannes

AU - Hegewisch-Bcker, Susanna

AU - Rivoltini, Licia

AU - Thiel, Eckhard

AU - Keilholz, Ulrich

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N2 - 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.

AB - 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.

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