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Cytotoxic tumour-infiltrating T lymphocytes influence outcome in resected pancreatic ductal adenocarcinoma

We studied the prognostic effect of CD3-, CD8- and CD103-positive T lymphocytes in a cohort of 165 patients with resected pancreatic ductal adenocarcinomas (PDACs) of the treatment group (adjuvant gemcitabine) and the untreated control group of the CONKO-001 study. Immunohistochemical stainings on t...

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Published in:European journal of cancer (1990) 2017-09, Vol.83, p.290-301
Main Authors: Lohneis, Philipp, Sinn, Marianne, Bischoff, Sven, Jühling, Anja, Pelzer, Uwe, Wislocka, Lilianna, Bahra, Marcus, Sinn, Bruno V., Denkert, Carsten, Oettle, Helmut, Bläker, Hendrik, Riess, Hanno, Jöhrens, Korinna, Striefler, Jana K.
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container_title European journal of cancer (1990)
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creator Lohneis, Philipp
Sinn, Marianne
Bischoff, Sven
Jühling, Anja
Pelzer, Uwe
Wislocka, Lilianna
Bahra, Marcus
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Oettle, Helmut
Bläker, Hendrik
Riess, Hanno
Jöhrens, Korinna
Striefler, Jana K.
description We studied the prognostic effect of CD3-, CD8- and CD103-positive T lymphocytes in a cohort of 165 patients with resected pancreatic ductal adenocarcinomas (PDACs) of the treatment group (adjuvant gemcitabine) and the untreated control group of the CONKO-001 study. Immunohistochemical stainings on tissue microarrays (TMAs) against CD3, CD8 and CD103 were performed according to standard procedures. A high number of CD8-positive lymphocytes were significantly and independently associated with longer disease-free survival (DFS) and overall survival (OS) in the overall study population. Median DFS/OS were 7.4/18.1 months for patients with a low number of CD8-positive intratumoural lymphocytes (≤42 per 1 mm tissue core) and 12.7/25.2 months for patients with high numbers (>42 per 1-mm tissue core; p = 0.008/0.020; HR 0.62/0.65). The ratio of intraepithelial to total CD103-positive lymphocytes, but not total numbers of CD103-positive lymphocytes or CD103-positive intraepithelial lymphocytes, was associated with significantly improved DFS and OS in the overall study population (p = 0.022/0.009). Median DFS/OS was 5.9/15.7 for patients with a ratio of intraepithelial to total CD103-positive intratumoural lymphocytes higher than 0.3 and 11.6/24.7 for patients with a lower ratio. T-lymphocyte subpopulations might be prognostic in resectable PDAC but need standardization and verification by further studies. •The prognostic effects of lymphocyte subpopulations were studied in patients with pancreatic carcinoma (PDAC).•A high number of CD8-positive lymphocytes are associated with longer in PDAC.•The ratio of intraepithelial to total CD103-positive lymphocytes is associated with longer DFS and OS in PDAC.
doi_str_mv 10.1016/j.ejca.2017.06.016
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Immunohistochemical stainings on tissue microarrays (TMAs) against CD3, CD8 and CD103 were performed according to standard procedures. A high number of CD8-positive lymphocytes were significantly and independently associated with longer disease-free survival (DFS) and overall survival (OS) in the overall study population. Median DFS/OS were 7.4/18.1 months for patients with a low number of CD8-positive intratumoural lymphocytes (≤42 per 1 mm tissue core) and 12.7/25.2 months for patients with high numbers (&gt;42 per 1-mm tissue core; p = 0.008/0.020; HR 0.62/0.65). The ratio of intraepithelial to total CD103-positive lymphocytes, but not total numbers of CD103-positive lymphocytes or CD103-positive intraepithelial lymphocytes, was associated with significantly improved DFS and OS in the overall study population (p = 0.022/0.009). 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T-lymphocyte subpopulations might be prognostic in resectable PDAC but need standardization and verification by further studies. •The prognostic effects of lymphocyte subpopulations were studied in patients with pancreatic carcinoma (PDAC).•A high number of CD8-positive lymphocytes are associated with longer in PDAC.•The ratio of intraepithelial to total CD103-positive lymphocytes is associated with longer DFS and OS in PDAC.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2017.06.016</identifier><identifier>PMID: 28772128</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adenocarcinoma ; Adult ; Aged ; Aged, 80 and over ; Antimetabolites, Antineoplastic - therapeutic use ; Carcinoma, Pancreatic Ductal - immunology ; Carcinoma, Pancreatic Ductal - pathology ; Carcinoma, Pancreatic Ductal - therapy ; CD103 ; CD103 antigen ; CD3 ; CD3 antigen ; CD3 Complex - metabolism ; CD8 ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Cytotoxicity ; Deoxycytidine - analogs &amp; derivatives ; Deoxycytidine - therapeutic use ; Disease-Free Survival ; Female ; Gemcitabine ; Humans ; Immunohistochemistry ; Integrin beta4 - analysis ; Lymphocytes ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating - immunology ; Male ; Middle Aged ; Pancreas ; Pancreatic cancer ; Pancreatic Neoplasms - immunology ; Pancreatic Neoplasms - pathology ; Pancreatic Neoplasms - therapy ; Patients ; Population studies ; Prognosis ; Standardization ; Subpopulations ; Survival ; T lymphocytes ; T-Lymphocytes, Cytotoxic - immunology ; Tumors ; Tumour-infiltrating lymphocytes</subject><ispartof>European journal of cancer (1990), 2017-09, Vol.83, p.290-301</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. 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Immunohistochemical stainings on tissue microarrays (TMAs) against CD3, CD8 and CD103 were performed according to standard procedures. A high number of CD8-positive lymphocytes were significantly and independently associated with longer disease-free survival (DFS) and overall survival (OS) in the overall study population. Median DFS/OS were 7.4/18.1 months for patients with a low number of CD8-positive intratumoural lymphocytes (≤42 per 1 mm tissue core) and 12.7/25.2 months for patients with high numbers (&gt;42 per 1-mm tissue core; p = 0.008/0.020; HR 0.62/0.65). The ratio of intraepithelial to total CD103-positive lymphocytes, but not total numbers of CD103-positive lymphocytes or CD103-positive intraepithelial lymphocytes, was associated with significantly improved DFS and OS in the overall study population (p = 0.022/0.009). Median DFS/OS was 5.9/15.7 for patients with a ratio of intraepithelial to total CD103-positive intratumoural lymphocytes higher than 0.3 and 11.6/24.7 for patients with a lower ratio. T-lymphocyte subpopulations might be prognostic in resectable PDAC but need standardization and verification by further studies. •The prognostic effects of lymphocyte subpopulations were studied in patients with pancreatic carcinoma (PDAC).•A high number of CD8-positive lymphocytes are associated with longer in PDAC.•The ratio of intraepithelial to total CD103-positive lymphocytes is associated with longer DFS and OS in PDAC.</description><subject>Adenocarcinoma</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antimetabolites, Antineoplastic - therapeutic use</subject><subject>Carcinoma, Pancreatic Ductal - immunology</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Carcinoma, Pancreatic Ductal - therapy</subject><subject>CD103</subject><subject>CD103 antigen</subject><subject>CD3</subject><subject>CD3 antigen</subject><subject>CD3 Complex - metabolism</subject><subject>CD8</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cytotoxicity</subject><subject>Deoxycytidine - analogs &amp; 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Immunohistochemical stainings on tissue microarrays (TMAs) against CD3, CD8 and CD103 were performed according to standard procedures. A high number of CD8-positive lymphocytes were significantly and independently associated with longer disease-free survival (DFS) and overall survival (OS) in the overall study population. Median DFS/OS were 7.4/18.1 months for patients with a low number of CD8-positive intratumoural lymphocytes (≤42 per 1 mm tissue core) and 12.7/25.2 months for patients with high numbers (&gt;42 per 1-mm tissue core; p = 0.008/0.020; HR 0.62/0.65). The ratio of intraepithelial to total CD103-positive lymphocytes, but not total numbers of CD103-positive lymphocytes or CD103-positive intraepithelial lymphocytes, was associated with significantly improved DFS and OS in the overall study population (p = 0.022/0.009). Median DFS/OS was 5.9/15.7 for patients with a ratio of intraepithelial to total CD103-positive intratumoural lymphocytes higher than 0.3 and 11.6/24.7 for patients with a lower ratio. T-lymphocyte subpopulations might be prognostic in resectable PDAC but need standardization and verification by further studies. •The prognostic effects of lymphocyte subpopulations were studied in patients with pancreatic carcinoma (PDAC).•A high number of CD8-positive lymphocytes are associated with longer in PDAC.•The ratio of intraepithelial to total CD103-positive lymphocytes is associated with longer DFS and OS in PDAC.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28772128</pmid><doi>10.1016/j.ejca.2017.06.016</doi><tpages>12</tpages></addata></record>
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subjects Adenocarcinoma
Adult
Aged
Aged, 80 and over
Antimetabolites, Antineoplastic - therapeutic use
Carcinoma, Pancreatic Ductal - immunology
Carcinoma, Pancreatic Ductal - pathology
Carcinoma, Pancreatic Ductal - therapy
CD103
CD103 antigen
CD3
CD3 antigen
CD3 Complex - metabolism
CD8
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cytotoxicity
Deoxycytidine - analogs & derivatives
Deoxycytidine - therapeutic use
Disease-Free Survival
Female
Gemcitabine
Humans
Immunohistochemistry
Integrin beta4 - analysis
Lymphocytes
Lymphocytes T
Lymphocytes, Tumor-Infiltrating - immunology
Male
Middle Aged
Pancreas
Pancreatic cancer
Pancreatic Neoplasms - immunology
Pancreatic Neoplasms - pathology
Pancreatic Neoplasms - therapy
Patients
Population studies
Prognosis
Standardization
Subpopulations
Survival
T lymphocytes
T-Lymphocytes, Cytotoxic - immunology
Tumors
Tumour-infiltrating lymphocytes
title Cytotoxic tumour-infiltrating T lymphocytes influence outcome in resected pancreatic ductal adenocarcinoma
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