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Expression of Programmed Cell Death Protein 1 by Tumor-Infiltrating Lymphocytes and Tumor Cells is Associated with Advanced Tumor Stage in Patients with Esophageal Adenocarcinoma
BACKGROUND: Despite recent advances in the therapy for adenocarcinoma of the esophagogastric junction (AEG), overall prognosis remains poor. Programmed cell death protein 1 (PD1) is a co-inhibitory receptor primarily expressed by T-cells. Tumor cells can escape anticancer immune responses by trigger...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539275/ https://www.ncbi.nlm.nih.gov/pubmed/28429196 http://dx.doi.org/10.1245/s10434-017-5858-7 |
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author | Kollmann, Dagmar Ignatova, Desislava Jedamzik, Julia Chang, Yun-Tsan Jomrich, Gerd Paireder, Matthias Kristo, Ivan Kazakov, Dmitry Michal, Michal Cozzio, Antonio Hoetzenecker, Wolfram Schatton, Tobias Asari, Reza Preusser, Matthias Guenova, Emmanuella Schoppmann, Sebastian F. |
author_facet | Kollmann, Dagmar Ignatova, Desislava Jedamzik, Julia Chang, Yun-Tsan Jomrich, Gerd Paireder, Matthias Kristo, Ivan Kazakov, Dmitry Michal, Michal Cozzio, Antonio Hoetzenecker, Wolfram Schatton, Tobias Asari, Reza Preusser, Matthias Guenova, Emmanuella Schoppmann, Sebastian F. |
author_sort | Kollmann, Dagmar |
collection | PubMed |
description | BACKGROUND: Despite recent advances in the therapy for adenocarcinoma of the esophagogastric junction (AEG), overall prognosis remains poor. Programmed cell death protein 1 (PD1) is a co-inhibitory receptor primarily expressed by T-cells. Tumor cells can escape anticancer immune responses by triggering the PD1 pathway. Moreover, PD1 receptor engagement on cancer cells may trigger tumor-intrinsic growth signals. This study aimed to evaluate the potential clinical relevance of PD1 expression by tumor-infiltrating lymphocytes (TILs) and cancer cells in the AEG. METHODS: Patients with AEG who underwent esophagectomy from 1992 to 2011 were included in the study. Expression of PD1was evaluated by immunohistochemistry and correlated with long-term overall survival (OS), disease-free survival (DFS), and various clinicopathologic parameters. RESULTS: Tumor biospecimens from 168 patients were analyzed. In the analysis, 81% of the patients showed high tumoral frequencies (>5%) of PD1-expressing TILs (TIL-PD1(+)), and 77% of patient tumors harbored high levels (>5%) of PD1(+) cancer cells (cancer-PD1(+)). Expression of PD1 by TILs and cancer cells correlated significantly (p < 0.05) with patients’ tumor stage and lymph node involvement. Compared with the patients who had low tumoral frequencies of PD1(+) TILs or cancer cells, the TIL-PD1(+) and cancer-PD1(+) patients demonstrated significantly reduced DFS in the univariate analysis (5-year DFS: 73.3 vs. 41.9%, log-rank 0.008 and 71.3 vs. 41.6%, p = 0.008, respectively). Additionally, the cancer-PD1(+) patients showed significantly decreased OS in the univariate analysis compared with the cancer-PD1(−) patients (5-year OS: 68.8 vs. 43.5%; p = 0.047). However, these correlations did not reach significance in the multivariate analysis. CONCLUSIONS: The PD1 receptor is expressed by both TILs and cancer cells in AEG. High expression of PD1 is associated with advanced tumor stage and lymph node involvement, but not with survival. |
format | Online Article Text |
id | pubmed-5539275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-55392752017-08-17 Expression of Programmed Cell Death Protein 1 by Tumor-Infiltrating Lymphocytes and Tumor Cells is Associated with Advanced Tumor Stage in Patients with Esophageal Adenocarcinoma Kollmann, Dagmar Ignatova, Desislava Jedamzik, Julia Chang, Yun-Tsan Jomrich, Gerd Paireder, Matthias Kristo, Ivan Kazakov, Dmitry Michal, Michal Cozzio, Antonio Hoetzenecker, Wolfram Schatton, Tobias Asari, Reza Preusser, Matthias Guenova, Emmanuella Schoppmann, Sebastian F. Ann Surg Oncol Gastrointestinal Oncology BACKGROUND: Despite recent advances in the therapy for adenocarcinoma of the esophagogastric junction (AEG), overall prognosis remains poor. Programmed cell death protein 1 (PD1) is a co-inhibitory receptor primarily expressed by T-cells. Tumor cells can escape anticancer immune responses by triggering the PD1 pathway. Moreover, PD1 receptor engagement on cancer cells may trigger tumor-intrinsic growth signals. This study aimed to evaluate the potential clinical relevance of PD1 expression by tumor-infiltrating lymphocytes (TILs) and cancer cells in the AEG. METHODS: Patients with AEG who underwent esophagectomy from 1992 to 2011 were included in the study. Expression of PD1was evaluated by immunohistochemistry and correlated with long-term overall survival (OS), disease-free survival (DFS), and various clinicopathologic parameters. RESULTS: Tumor biospecimens from 168 patients were analyzed. In the analysis, 81% of the patients showed high tumoral frequencies (>5%) of PD1-expressing TILs (TIL-PD1(+)), and 77% of patient tumors harbored high levels (>5%) of PD1(+) cancer cells (cancer-PD1(+)). Expression of PD1 by TILs and cancer cells correlated significantly (p < 0.05) with patients’ tumor stage and lymph node involvement. Compared with the patients who had low tumoral frequencies of PD1(+) TILs or cancer cells, the TIL-PD1(+) and cancer-PD1(+) patients demonstrated significantly reduced DFS in the univariate analysis (5-year DFS: 73.3 vs. 41.9%, log-rank 0.008 and 71.3 vs. 41.6%, p = 0.008, respectively). Additionally, the cancer-PD1(+) patients showed significantly decreased OS in the univariate analysis compared with the cancer-PD1(−) patients (5-year OS: 68.8 vs. 43.5%; p = 0.047). However, these correlations did not reach significance in the multivariate analysis. CONCLUSIONS: The PD1 receptor is expressed by both TILs and cancer cells in AEG. High expression of PD1 is associated with advanced tumor stage and lymph node involvement, but not with survival. Springer International Publishing 2017-04-20 2017 /pmc/articles/PMC5539275/ /pubmed/28429196 http://dx.doi.org/10.1245/s10434-017-5858-7 Text en © The Author(s) 2017 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. |
spellingShingle | Gastrointestinal Oncology Kollmann, Dagmar Ignatova, Desislava Jedamzik, Julia Chang, Yun-Tsan Jomrich, Gerd Paireder, Matthias Kristo, Ivan Kazakov, Dmitry Michal, Michal Cozzio, Antonio Hoetzenecker, Wolfram Schatton, Tobias Asari, Reza Preusser, Matthias Guenova, Emmanuella Schoppmann, Sebastian F. Expression of Programmed Cell Death Protein 1 by Tumor-Infiltrating Lymphocytes and Tumor Cells is Associated with Advanced Tumor Stage in Patients with Esophageal Adenocarcinoma |
title | Expression of Programmed Cell Death Protein 1 by Tumor-Infiltrating Lymphocytes and Tumor Cells is Associated with Advanced Tumor Stage in Patients with Esophageal Adenocarcinoma |
title_full | Expression of Programmed Cell Death Protein 1 by Tumor-Infiltrating Lymphocytes and Tumor Cells is Associated with Advanced Tumor Stage in Patients with Esophageal Adenocarcinoma |
title_fullStr | Expression of Programmed Cell Death Protein 1 by Tumor-Infiltrating Lymphocytes and Tumor Cells is Associated with Advanced Tumor Stage in Patients with Esophageal Adenocarcinoma |
title_full_unstemmed | Expression of Programmed Cell Death Protein 1 by Tumor-Infiltrating Lymphocytes and Tumor Cells is Associated with Advanced Tumor Stage in Patients with Esophageal Adenocarcinoma |
title_short | Expression of Programmed Cell Death Protein 1 by Tumor-Infiltrating Lymphocytes and Tumor Cells is Associated with Advanced Tumor Stage in Patients with Esophageal Adenocarcinoma |
title_sort | expression of programmed cell death protein 1 by tumor-infiltrating lymphocytes and tumor cells is associated with advanced tumor stage in patients with esophageal adenocarcinoma |
topic | Gastrointestinal Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539275/ https://www.ncbi.nlm.nih.gov/pubmed/28429196 http://dx.doi.org/10.1245/s10434-017-5858-7 |
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