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Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer

BACKGROUND: Tapasin is a crucial component of the major histocompatibility (MHC) class I antigen presentation pathway. Defects in this pathway can lead to tumor immune evasion. The aim of this study was to test whether tapasin expression correlates with CD8(+) cytotoxic T lymphocyte (CTL) infiltrati...

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Autores principales: Sokol, Lena, Koelzer, Viktor H., Rau, Tilman T., Karamitopoulou, Eva, Zlobec, Inti, Lugli, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551690/
https://www.ncbi.nlm.nih.gov/pubmed/26310568
http://dx.doi.org/10.1186/s12967-015-0647-1
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author Sokol, Lena
Koelzer, Viktor H.
Rau, Tilman T.
Karamitopoulou, Eva
Zlobec, Inti
Lugli, Alessandro
author_facet Sokol, Lena
Koelzer, Viktor H.
Rau, Tilman T.
Karamitopoulou, Eva
Zlobec, Inti
Lugli, Alessandro
author_sort Sokol, Lena
collection PubMed
description BACKGROUND: Tapasin is a crucial component of the major histocompatibility (MHC) class I antigen presentation pathway. Defects in this pathway can lead to tumor immune evasion. The aim of this study was to test whether tapasin expression correlates with CD8(+) cytotoxic T lymphocyte (CTL) infiltration of colorectal cancer (CRC) and overall survival. METHODS: A next-generation tissue microarray (ngTMA) of 198 CRC patients with full clinicopathological information was included in this study. TMA slides were immunostained for tapasin, MHC I and CD8. Marker expression was analyzed with immune-cell infiltration, patient survival and TNM-staging. RESULTS: A reduction of tapasin expression strongly correlated with venous invasion (AUC 0.682, OR 2.7, p = 0.002; 95 % CI 1.7–5.0), lymphatic invasion (AUC 0.620, OR 2.0, p = 0.005; 95 % CI 1.3–3.3), distant metastasis (AUC 0.727, OR 2.9, p = 0.004; 95 % CI 1.4–5.9) and an infiltrative tumor border configuration (AUC 0.621, OR 2.2, p = 0.017; 95 % CI 1.2–4.4). Further, tapasin expression was associated with CD8(+) CTL infiltration (AUC 0.729, OR 5.4, p < 0.001; 95 % CI 2.6–11), and favorable overall survival (p = 0.004, HR 0.6, 95 % CI 0.42–0.85). CONCLUSIONS: Consistent with published functional data showing that tapasin promotes antigen presentation, as well as tumor immune recognition and destruction by CD8(+) CTLs, a reduction in tapasin expression is associated with tumor progression in CRC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0647-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-45516902015-08-29 Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer Sokol, Lena Koelzer, Viktor H. Rau, Tilman T. Karamitopoulou, Eva Zlobec, Inti Lugli, Alessandro J Transl Med Research BACKGROUND: Tapasin is a crucial component of the major histocompatibility (MHC) class I antigen presentation pathway. Defects in this pathway can lead to tumor immune evasion. The aim of this study was to test whether tapasin expression correlates with CD8(+) cytotoxic T lymphocyte (CTL) infiltration of colorectal cancer (CRC) and overall survival. METHODS: A next-generation tissue microarray (ngTMA) of 198 CRC patients with full clinicopathological information was included in this study. TMA slides were immunostained for tapasin, MHC I and CD8. Marker expression was analyzed with immune-cell infiltration, patient survival and TNM-staging. RESULTS: A reduction of tapasin expression strongly correlated with venous invasion (AUC 0.682, OR 2.7, p = 0.002; 95 % CI 1.7–5.0), lymphatic invasion (AUC 0.620, OR 2.0, p = 0.005; 95 % CI 1.3–3.3), distant metastasis (AUC 0.727, OR 2.9, p = 0.004; 95 % CI 1.4–5.9) and an infiltrative tumor border configuration (AUC 0.621, OR 2.2, p = 0.017; 95 % CI 1.2–4.4). Further, tapasin expression was associated with CD8(+) CTL infiltration (AUC 0.729, OR 5.4, p < 0.001; 95 % CI 2.6–11), and favorable overall survival (p = 0.004, HR 0.6, 95 % CI 0.42–0.85). CONCLUSIONS: Consistent with published functional data showing that tapasin promotes antigen presentation, as well as tumor immune recognition and destruction by CD8(+) CTLs, a reduction in tapasin expression is associated with tumor progression in CRC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0647-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-08-27 /pmc/articles/PMC4551690/ /pubmed/26310568 http://dx.doi.org/10.1186/s12967-015-0647-1 Text en © Sokol et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sokol, Lena
Koelzer, Viktor H.
Rau, Tilman T.
Karamitopoulou, Eva
Zlobec, Inti
Lugli, Alessandro
Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer
title Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer
title_full Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer
title_fullStr Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer
title_full_unstemmed Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer
title_short Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer
title_sort loss of tapasin correlates with diminished cd8(+) t-cell immunity and prognosis in colorectal cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551690/
https://www.ncbi.nlm.nih.gov/pubmed/26310568
http://dx.doi.org/10.1186/s12967-015-0647-1
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