Cargando…
NKG2D ligand tumor expression and association with clinical outcome in early breast cancer patients: an observational study
BACKGROUND: Cell surface NKG2D ligands (NKG2DL) bind to the activating NKG2D receptor present on NK cells and subsets of T cells, thus playing a role in initiating an immune response. We examined tumor expression and prognostic effect of NKG2DL in breast cancer patients. METHODS: Our study populatio...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292504/ https://www.ncbi.nlm.nih.gov/pubmed/22257486 http://dx.doi.org/10.1186/1471-2407-12-24 |
_version_ | 1782225286467682304 |
---|---|
author | de Kruijf, Esther M Sajet, Anita van Nes, Johanna GH Putter, Hein Smit, Vincent THBM Eagle, Robert A Jafferji, Insiya Trowsdale, John Liefers, Gerrit Jan van de Velde, Cornelis JH Kuppen, Peter JK |
author_facet | de Kruijf, Esther M Sajet, Anita van Nes, Johanna GH Putter, Hein Smit, Vincent THBM Eagle, Robert A Jafferji, Insiya Trowsdale, John Liefers, Gerrit Jan van de Velde, Cornelis JH Kuppen, Peter JK |
author_sort | de Kruijf, Esther M |
collection | PubMed |
description | BACKGROUND: Cell surface NKG2D ligands (NKG2DL) bind to the activating NKG2D receptor present on NK cells and subsets of T cells, thus playing a role in initiating an immune response. We examined tumor expression and prognostic effect of NKG2DL in breast cancer patients. METHODS: Our study population (n = 677) consisted of all breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Formalin-fixed paraffin-embedded tumor tissue was immunohistochemically stained with antibodies directed against MIC-A/MIC-B (MIC-AB), ULBP-1, ULBP-2, ULBP-3, ULBP-4, and ULBP-5. RESULTS: NKG2DL were frequently expressed by tumors (MIC-AB, 50% of the cases; ULBP-1, 90%; ULBP-2, 99%; ULBP-3, 100%; ULBP-4, 26%; ULBP-5, 90%) and often showed co-expression: MIC-AB and ULBP-4 (p = 0.043), ULBP-1 and ULBP-5 (p = 0.006), ULBP-4 and ULBP-5 (p < 0.001). MIC-AB (p = 0.001) and ULBP-2 (p = 0.006) expression resulted in a statistically significant longer relapse free period (RFP). Combined expression of these ligands showed to be an independent prognostic parameter for RFP (p < 0.001, HR 0.41). Combined expression of all ligands showed no associations with clinical outcome. CONCLUSIONS: We demonstrated for the first time that NKG2DL are frequently expressed and often co-expressed in breast cancer. Expression of MIC-AB and ULBP-2 resulted in a statistically significant beneficial outcome concerning RFP with high discriminative power. Combination of all NKG2DL showed no additive or interactive effect of ligands on each other, suggesting that similar and co-operative functioning of all NKG2DL can not be assumed. Our observations suggest that among driving forces in breast cancer outcome are immune activation on one site and tumor immune escape on the other site. |
format | Online Article Text |
id | pubmed-3292504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32925042012-03-03 NKG2D ligand tumor expression and association with clinical outcome in early breast cancer patients: an observational study de Kruijf, Esther M Sajet, Anita van Nes, Johanna GH Putter, Hein Smit, Vincent THBM Eagle, Robert A Jafferji, Insiya Trowsdale, John Liefers, Gerrit Jan van de Velde, Cornelis JH Kuppen, Peter JK BMC Cancer Research Article BACKGROUND: Cell surface NKG2D ligands (NKG2DL) bind to the activating NKG2D receptor present on NK cells and subsets of T cells, thus playing a role in initiating an immune response. We examined tumor expression and prognostic effect of NKG2DL in breast cancer patients. METHODS: Our study population (n = 677) consisted of all breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Formalin-fixed paraffin-embedded tumor tissue was immunohistochemically stained with antibodies directed against MIC-A/MIC-B (MIC-AB), ULBP-1, ULBP-2, ULBP-3, ULBP-4, and ULBP-5. RESULTS: NKG2DL were frequently expressed by tumors (MIC-AB, 50% of the cases; ULBP-1, 90%; ULBP-2, 99%; ULBP-3, 100%; ULBP-4, 26%; ULBP-5, 90%) and often showed co-expression: MIC-AB and ULBP-4 (p = 0.043), ULBP-1 and ULBP-5 (p = 0.006), ULBP-4 and ULBP-5 (p < 0.001). MIC-AB (p = 0.001) and ULBP-2 (p = 0.006) expression resulted in a statistically significant longer relapse free period (RFP). Combined expression of these ligands showed to be an independent prognostic parameter for RFP (p < 0.001, HR 0.41). Combined expression of all ligands showed no associations with clinical outcome. CONCLUSIONS: We demonstrated for the first time that NKG2DL are frequently expressed and often co-expressed in breast cancer. Expression of MIC-AB and ULBP-2 resulted in a statistically significant beneficial outcome concerning RFP with high discriminative power. Combination of all NKG2DL showed no additive or interactive effect of ligands on each other, suggesting that similar and co-operative functioning of all NKG2DL can not be assumed. Our observations suggest that among driving forces in breast cancer outcome are immune activation on one site and tumor immune escape on the other site. BioMed Central 2012-01-18 /pmc/articles/PMC3292504/ /pubmed/22257486 http://dx.doi.org/10.1186/1471-2407-12-24 Text en Copyright ©2012 de Kruijf et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article de Kruijf, Esther M Sajet, Anita van Nes, Johanna GH Putter, Hein Smit, Vincent THBM Eagle, Robert A Jafferji, Insiya Trowsdale, John Liefers, Gerrit Jan van de Velde, Cornelis JH Kuppen, Peter JK NKG2D ligand tumor expression and association with clinical outcome in early breast cancer patients: an observational study |
title | NKG2D ligand tumor expression and association with clinical outcome in early breast cancer patients: an observational study |
title_full | NKG2D ligand tumor expression and association with clinical outcome in early breast cancer patients: an observational study |
title_fullStr | NKG2D ligand tumor expression and association with clinical outcome in early breast cancer patients: an observational study |
title_full_unstemmed | NKG2D ligand tumor expression and association with clinical outcome in early breast cancer patients: an observational study |
title_short | NKG2D ligand tumor expression and association with clinical outcome in early breast cancer patients: an observational study |
title_sort | nkg2d ligand tumor expression and association with clinical outcome in early breast cancer patients: an observational study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292504/ https://www.ncbi.nlm.nih.gov/pubmed/22257486 http://dx.doi.org/10.1186/1471-2407-12-24 |
work_keys_str_mv | AT dekruijfestherm nkg2dligandtumorexpressionandassociationwithclinicaloutcomeinearlybreastcancerpatientsanobservationalstudy AT sajetanita nkg2dligandtumorexpressionandassociationwithclinicaloutcomeinearlybreastcancerpatientsanobservationalstudy AT vannesjohannagh nkg2dligandtumorexpressionandassociationwithclinicaloutcomeinearlybreastcancerpatientsanobservationalstudy AT putterhein nkg2dligandtumorexpressionandassociationwithclinicaloutcomeinearlybreastcancerpatientsanobservationalstudy AT smitvincentthbm nkg2dligandtumorexpressionandassociationwithclinicaloutcomeinearlybreastcancerpatientsanobservationalstudy AT eagleroberta nkg2dligandtumorexpressionandassociationwithclinicaloutcomeinearlybreastcancerpatientsanobservationalstudy AT jafferjiinsiya nkg2dligandtumorexpressionandassociationwithclinicaloutcomeinearlybreastcancerpatientsanobservationalstudy AT trowsdalejohn nkg2dligandtumorexpressionandassociationwithclinicaloutcomeinearlybreastcancerpatientsanobservationalstudy AT liefersgerritjan nkg2dligandtumorexpressionandassociationwithclinicaloutcomeinearlybreastcancerpatientsanobservationalstudy AT vandeveldecornelisjh nkg2dligandtumorexpressionandassociationwithclinicaloutcomeinearlybreastcancerpatientsanobservationalstudy AT kuppenpeterjk nkg2dligandtumorexpressionandassociationwithclinicaloutcomeinearlybreastcancerpatientsanobservationalstudy |