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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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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. |
format | Online Article Text |
id | pubmed-4551690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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