Research

Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients

Sebastian Ochsenreither¹ , Alberto Fusi¹ , Susanne Wojtke¹ , Antonia Busse¹ , Natascha C Nüssler² , Eckhard Thiel¹ , Ulrich Keilholz¹ and Dirk Nagorsen^1,3,4

¹  Charité, Campus Benjamin Franklin, Department of Hematology and Oncology, Hindenburgdamm 30, 12200 Berlin, Germany

²  Department of General and Visceral Surgery, Klinikum Neuperlach, Städtisches Klinikum München, Oskar-Maria-Graf Ring 51, 81737 Munich, Germany

³  University of Heidelberg, Medizinische Fakultät Mannheim, Department of Hematology/Oncology, Theodor-Kutzer-Ufer 1, 68167 Mannheim, Germany

⁴  Micromet AG, Staffelseestr 2, 81477 Munich, Germany

author email corresponding author email

Journal of Translational Medicine 2010, 8:35doi:10.1186/1479-5876-8-35

Published:	12 April 2010

Abstract

Several immunotherapeutic approaches rely on antigen-specific T-cells. Restrictions in the T-cell receptor (TCR) repertoire were reported as indicator of anti-tumor cytotoxic T-lymphocyte (CTL) response in various tumor entities. It is unclear yet whether a TCR restriction in peripheral blood mirrors the tumor compartment. We compared the expression of TCR Vβ-families for the quantification of TCR repertoire alterations in blood and tissue samples from patients with colorectal carcinoma. Blood samples from patients with colorectal carcinoma and healthy volunteers and tissue samples of normal colonic mucosa and colorectal carcinoma were analyzed. Relative Vβ-family quantification was performed based on quantitative reverse transcribed PCR. Standard deviation and average mean of the single families were determined. Two variables describing the degree of Vβ-repertoire restriction were defined. Forty-eight blood samples and 37 tissue samples were analyzed. TCR repertoire restriction was higher in blood of tumor patients than in blood of healthy controls (p < 0.05). No difference in the degree of TCR repertoire restriction was found between carcinoma and unaffected colon tissue. We found no corresponding elevated TCR families among the different compartments blood, normal colon, and carcinoma tissue of the same patient. In conclusion, we observed a repertoire restriction in peripheral blood as well as in tumor tissue of cancer patients. However, in tumor tissue, repertoire alterations were comparable to normal mucosa, suggesting compartment-specific TCR distribution rather than alterations due to tumor-T-cell interaction questioning the presence of highly restricted clonal T-cell expansions in colorectal cancer as they have been described in other, assumingly more immunogenic tumor entities.