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Characterising the prognostic potential of HLA-DR during colorectal cancer development
HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347515/ https://www.ncbi.nlm.nih.gov/pubmed/32306077 http://dx.doi.org/10.1007/s00262-020-02571-2 |
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author | Dunne, Margaret R. Phelan, James J. Michielsen, Adriana J. Maguire, Aoife A. Dunne, Cara Martin, Petra Noonan, Sinead Tosetto, Miriam Geraghty, Robert Fennelly, David Sheahan, Kieran Ryan, Elizabeth J. O’Sullivan, Jacintha |
author_facet | Dunne, Margaret R. Phelan, James J. Michielsen, Adriana J. Maguire, Aoife A. Dunne, Cara Martin, Petra Noonan, Sinead Tosetto, Miriam Geraghty, Robert Fennelly, David Sheahan, Kieran Ryan, Elizabeth J. O’Sullivan, Jacintha |
author_sort | Dunne, Margaret R. |
collection | PubMed |
description | HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma–adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as patients with lower expression. This association was significant for HLA-DR staining in the colorectal carcinoma epithelium (n = 152, p = 0.011, HR 1.9, 95% CI 1.15–3.15) and adjacent non-neoplastic epithelium (n = 152, p < 0.001, HR 2.7, 95% CI 1.59–4.66), but not stroma. In stage II cases, however, the prognostic value of HLA-DR expression was significant only in adjacent non-neoplastic tissues, for both epithelium (n = 63, p = 0.015, HR 3.6, 95% CI 1.279–10.25) and stroma (n = 63, p = 0.018, HR 5.07, 95% CI 1.32–19.49). HLA-DR was lower in carcinoma tissue compared to matched adenomas (n = 35), in epithelium (p < 0.01) and stroma (p < 0.001). HLA-DR was further reduced in late-stage carcinoma (n = 101) compared to early stage (n = 105), in epithelium (p < 0.001) and stroma (p < 0.01). HLA-DR expression was lower (p < 0.05) in the adjacent non-neoplastic epithelium of patients with cancer recurrence. We demonstrate a progressive loss of HLA-DR in epithelial and stromal tissue compartments during CRC development and show prognostic ability in carcinoma–adjacent non-neoplastic tissues, highlighting the importance of this molecule in the anti-cancer immune response. These findings may have wider implications for immunotherapeutic interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-020-02571-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7347515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-73475152020-07-13 Characterising the prognostic potential of HLA-DR during colorectal cancer development Dunne, Margaret R. Phelan, James J. Michielsen, Adriana J. Maguire, Aoife A. Dunne, Cara Martin, Petra Noonan, Sinead Tosetto, Miriam Geraghty, Robert Fennelly, David Sheahan, Kieran Ryan, Elizabeth J. O’Sullivan, Jacintha Cancer Immunol Immunother Original Article HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma–adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as patients with lower expression. This association was significant for HLA-DR staining in the colorectal carcinoma epithelium (n = 152, p = 0.011, HR 1.9, 95% CI 1.15–3.15) and adjacent non-neoplastic epithelium (n = 152, p < 0.001, HR 2.7, 95% CI 1.59–4.66), but not stroma. In stage II cases, however, the prognostic value of HLA-DR expression was significant only in adjacent non-neoplastic tissues, for both epithelium (n = 63, p = 0.015, HR 3.6, 95% CI 1.279–10.25) and stroma (n = 63, p = 0.018, HR 5.07, 95% CI 1.32–19.49). HLA-DR was lower in carcinoma tissue compared to matched adenomas (n = 35), in epithelium (p < 0.01) and stroma (p < 0.001). HLA-DR was further reduced in late-stage carcinoma (n = 101) compared to early stage (n = 105), in epithelium (p < 0.001) and stroma (p < 0.01). HLA-DR expression was lower (p < 0.05) in the adjacent non-neoplastic epithelium of patients with cancer recurrence. We demonstrate a progressive loss of HLA-DR in epithelial and stromal tissue compartments during CRC development and show prognostic ability in carcinoma–adjacent non-neoplastic tissues, highlighting the importance of this molecule in the anti-cancer immune response. These findings may have wider implications for immunotherapeutic interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-020-02571-2) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-04-18 2020 /pmc/articles/PMC7347515/ /pubmed/32306077 http://dx.doi.org/10.1007/s00262-020-02571-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Article Dunne, Margaret R. Phelan, James J. Michielsen, Adriana J. Maguire, Aoife A. Dunne, Cara Martin, Petra Noonan, Sinead Tosetto, Miriam Geraghty, Robert Fennelly, David Sheahan, Kieran Ryan, Elizabeth J. O’Sullivan, Jacintha Characterising the prognostic potential of HLA-DR during colorectal cancer development |
title | Characterising the prognostic potential of HLA-DR during colorectal cancer development |
title_full | Characterising the prognostic potential of HLA-DR during colorectal cancer development |
title_fullStr | Characterising the prognostic potential of HLA-DR during colorectal cancer development |
title_full_unstemmed | Characterising the prognostic potential of HLA-DR during colorectal cancer development |
title_short | Characterising the prognostic potential of HLA-DR during colorectal cancer development |
title_sort | characterising the prognostic potential of hla-dr during colorectal cancer development |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347515/ https://www.ncbi.nlm.nih.gov/pubmed/32306077 http://dx.doi.org/10.1007/s00262-020-02571-2 |
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