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

<p>Abstract</p> <p>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 r...

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Main Authors: Thiel Eckhard, Nüssler Natascha C, Busse Antonia, Wojtke Susanne, Fusi Alberto, Ochsenreither Sebastian, Keilholz Ulrich, Nagorsen Dirk
Format: Article
Language:English
Published: BMC 2010-04-01
Series:Journal of Translational Medicine
Online Access:http://www.translational-medicine.com/content/8/1/35
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author Thiel Eckhard
Nüssler Natascha C
Busse Antonia
Wojtke Susanne
Fusi Alberto
Ochsenreither Sebastian
Keilholz Ulrich
Nagorsen Dirk
author_facet Thiel Eckhard
Nüssler Natascha C
Busse Antonia
Wojtke Susanne
Fusi Alberto
Ochsenreither Sebastian
Keilholz Ulrich
Nagorsen Dirk
author_sort Thiel Eckhard
collection DOAJ
description <p>Abstract</p> <p>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 <it>Vβ</it>-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 <it>Vβ</it>-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 <it>Vβ</it>-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 (<it>p </it>< 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.</p>
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spelling doaj.art-df85369712314efc99405ea8ceda573c2022-12-22T02:48:55ZengBMCJournal of Translational Medicine1479-58762010-04-01813510.1186/1479-5876-8-35Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patientsThiel EckhardNüssler Natascha CBusse AntoniaWojtke SusanneFusi AlbertoOchsenreither SebastianKeilholz UlrichNagorsen Dirk<p>Abstract</p> <p>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 <it>Vβ</it>-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 <it>Vβ</it>-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 <it>Vβ</it>-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 (<it>p </it>< 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.</p>http://www.translational-medicine.com/content/8/1/35
spellingShingle Thiel Eckhard
Nüssler Natascha C
Busse Antonia
Wojtke Susanne
Fusi Alberto
Ochsenreither Sebastian
Keilholz Ulrich
Nagorsen Dirk
Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients
Journal of Translational Medicine
title Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients
title_full Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients
title_fullStr Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients
title_full_unstemmed Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients
title_short Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients
title_sort comparison of t cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients
url http://www.translational-medicine.com/content/8/1/35
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