Cargando…
The positive prognostic effect of stromal CD8+ tumor-infiltrating T cells is restrained by the expression of HLA-E in non-small cell lung carcinoma
INTRODUCTION: Tumor-infiltrating CD8+ T cells are associated with improved clinical outcomes in non-small cell lung cancer (NSCLC). Here we studied their prognostic effect in the context of the expression of HLA molecules that are key in tumor recognition (HLA-A, B and C) or suppression of immunity...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823121/ https://www.ncbi.nlm.nih.gov/pubmed/26658106 http://dx.doi.org/10.18632/oncotarget.6506 |
_version_ | 1782425863513440256 |
---|---|
author | Yazdi, Mehrdad Talebian van Riet, Sander van Schadewijk, Annemarie Fiocco, Marta van Hall, Thorbald Taube, Christian Hiemstra, Pieter S. van der burg, Sjoerd H. |
author_facet | Yazdi, Mehrdad Talebian van Riet, Sander van Schadewijk, Annemarie Fiocco, Marta van Hall, Thorbald Taube, Christian Hiemstra, Pieter S. van der burg, Sjoerd H. |
author_sort | Yazdi, Mehrdad Talebian |
collection | PubMed |
description | INTRODUCTION: Tumor-infiltrating CD8+ T cells are associated with improved clinical outcomes in non-small cell lung cancer (NSCLC). Here we studied their prognostic effect in the context of the expression of HLA molecules that are key in tumor recognition (HLA-A, B and C) or suppression of immunity (HLA-E) as this is still unknown. METHODS: Tumor tissue of 197 patients with resected pulmonary adenocarcinoma was analyzed for the presence of CD8+ T cells and the expression of β2-microglobulin, HLA-A, HLA-B/C and HLA-E. The relation of these parameters with overall survival (OS) was assessed. RESULTS: Loss and low expression of HLA-A or HLA-B/C was found in 44% and 75% of cases respectively. A high CD8+ tumor infiltration was strongly associated with clinical benefit only when the tumors retained good expression of HLA-A and HLA-B/C (p=0.004). In addition, more than 70% of the tumors were found to display a high expression of HLA-E. The expression of HLA-E by tumor cells was an independent negative prognostic factor for OS (p=0.031). Importantly, a dense stromal CD8+ T cell infiltration was strongly associated with improved OS only in HLA-E negative tumors (p=0.005) and its prognostic effect was completely abolished when tumors highly expressed HLA-E (p=0.989). CONCLUSIONS: CD8+ T cell infiltration strongly contributes to a better prognosis in NSCLC when the tumor cells retain the expression of classical HLA class I and do not express HLA-E. Therefore, analysis of HLA-A, -B/C and HLA-E expression should be included as biomarkers to predict the response to immunotherapy. |
format | Online Article Text |
id | pubmed-4823121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-48231212016-05-03 The positive prognostic effect of stromal CD8+ tumor-infiltrating T cells is restrained by the expression of HLA-E in non-small cell lung carcinoma Yazdi, Mehrdad Talebian van Riet, Sander van Schadewijk, Annemarie Fiocco, Marta van Hall, Thorbald Taube, Christian Hiemstra, Pieter S. van der burg, Sjoerd H. Oncotarget Research Paper INTRODUCTION: Tumor-infiltrating CD8+ T cells are associated with improved clinical outcomes in non-small cell lung cancer (NSCLC). Here we studied their prognostic effect in the context of the expression of HLA molecules that are key in tumor recognition (HLA-A, B and C) or suppression of immunity (HLA-E) as this is still unknown. METHODS: Tumor tissue of 197 patients with resected pulmonary adenocarcinoma was analyzed for the presence of CD8+ T cells and the expression of β2-microglobulin, HLA-A, HLA-B/C and HLA-E. The relation of these parameters with overall survival (OS) was assessed. RESULTS: Loss and low expression of HLA-A or HLA-B/C was found in 44% and 75% of cases respectively. A high CD8+ tumor infiltration was strongly associated with clinical benefit only when the tumors retained good expression of HLA-A and HLA-B/C (p=0.004). In addition, more than 70% of the tumors were found to display a high expression of HLA-E. The expression of HLA-E by tumor cells was an independent negative prognostic factor for OS (p=0.031). Importantly, a dense stromal CD8+ T cell infiltration was strongly associated with improved OS only in HLA-E negative tumors (p=0.005) and its prognostic effect was completely abolished when tumors highly expressed HLA-E (p=0.989). CONCLUSIONS: CD8+ T cell infiltration strongly contributes to a better prognosis in NSCLC when the tumor cells retain the expression of classical HLA class I and do not express HLA-E. Therefore, analysis of HLA-A, -B/C and HLA-E expression should be included as biomarkers to predict the response to immunotherapy. Impact Journals LLC 2015-12-02 /pmc/articles/PMC4823121/ /pubmed/26658106 http://dx.doi.org/10.18632/oncotarget.6506 Text en Copyright: © 2016 Yazdi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Yazdi, Mehrdad Talebian van Riet, Sander van Schadewijk, Annemarie Fiocco, Marta van Hall, Thorbald Taube, Christian Hiemstra, Pieter S. van der burg, Sjoerd H. The positive prognostic effect of stromal CD8+ tumor-infiltrating T cells is restrained by the expression of HLA-E in non-small cell lung carcinoma |
title | The positive prognostic effect of stromal CD8+ tumor-infiltrating T cells is restrained by the expression of HLA-E in non-small cell lung carcinoma |
title_full | The positive prognostic effect of stromal CD8+ tumor-infiltrating T cells is restrained by the expression of HLA-E in non-small cell lung carcinoma |
title_fullStr | The positive prognostic effect of stromal CD8+ tumor-infiltrating T cells is restrained by the expression of HLA-E in non-small cell lung carcinoma |
title_full_unstemmed | The positive prognostic effect of stromal CD8+ tumor-infiltrating T cells is restrained by the expression of HLA-E in non-small cell lung carcinoma |
title_short | The positive prognostic effect of stromal CD8+ tumor-infiltrating T cells is restrained by the expression of HLA-E in non-small cell lung carcinoma |
title_sort | positive prognostic effect of stromal cd8+ tumor-infiltrating t cells is restrained by the expression of hla-e in non-small cell lung carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823121/ https://www.ncbi.nlm.nih.gov/pubmed/26658106 http://dx.doi.org/10.18632/oncotarget.6506 |
work_keys_str_mv | AT yazdimehrdadtalebian thepositiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT vanrietsander thepositiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT vanschadewijkannemarie thepositiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT fioccomarta thepositiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT vanhallthorbald thepositiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT taubechristian thepositiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT hiemstrapieters thepositiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT vanderburgsjoerdh thepositiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT yazdimehrdadtalebian positiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT vanrietsander positiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT vanschadewijkannemarie positiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT fioccomarta positiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT vanhallthorbald positiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT taubechristian positiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT hiemstrapieters positiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma AT vanderburgsjoerdh positiveprognosticeffectofstromalcd8tumorinfiltratingtcellsisrestrainedbytheexpressionofhlaeinnonsmallcelllungcarcinoma |