Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma

Pancreatic cancer features elaborate mechanisms of immune evasion. The potential of new immune molecules was explored to restore the antitumor immune response. If these immune molecules are associated with poor survival, specific drugs could take effect. Here, we analyze the expression of VISTA, LAG...

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Main Authors: Felix C. Popp, Ingracia Capino, Joana Bartels, Alexander Damanakis, Jiahui Li, Rabi R. Datta, Heike Löser, Yue Zhao, Alexander Quaas, Philipp Lohneis, Christiane J. Bruns, on behalf of the PANCALYZE Study Group
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Cancers
Subjects:
IDO
Online Access:https://www.mdpi.com/2072-6694/13/11/2689
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spelling doaj-6c49a7f497a44a8db306390c88eb15e02021-06-01T01:37:30ZengMDPI AGCancers2072-66942021-05-01132689268910.3390/cancers13112689Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal AdenocarcinomaFelix C. Popp0Ingracia Capino1Joana Bartels2Alexander Damanakis3Jiahui Li4Rabi R. Datta5Heike Löser6Yue Zhao7Alexander Quaas8Philipp Lohneis9Christiane J. Bruns10on behalf of the PANCALYZE Study GroupDepartment of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937 Cologne, GermanyDepartment of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937 Cologne, GermanyDepartment of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937 Cologne, GermanyDepartment of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937 Cologne, GermanyDepartment of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937 Cologne, GermanyDepartment of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937 Cologne, GermanyInstitute of Pathology, University of Cologne, 50937 Cologne, GermanyDepartment of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937 Cologne, GermanyInstitute of Pathology, University of Cologne, 50937 Cologne, GermanyInstitute of Pathology, University of Cologne, 50937 Cologne, GermanyDepartment of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937 Cologne, GermanyPancreatic cancer features elaborate mechanisms of immune evasion. The potential of new immune molecules was explored to restore the antitumor immune response. If these immune molecules are associated with poor survival, specific drugs could take effect. Here, we analyze the expression of VISTA, LAG3, IDO, and TIM3 on tumor-infiltrating lymphocytes (TILs) and its impact on patient survival. We analyzed 153 pancreatic cancer patients from the prospectively managed database of the multicentered PANCALYZE study. Immunohistochemistry on a tissue microarray assessed VISTA, LAG3, IDO, and TIM3 expression of TILs from the patients undergoing primary resection. Complementarily, we analyzed publicly available transcriptomic data (<i>n</i> = 903). Successful completion of chemotherapy, and lymph node status were independent predictors of survival in the multivariate analysis of the clinicopathologic parameters. Fifteen tumors were exclusively VISTA-positive, thirteen tumors expressed VISTA together with TIM3, and ten tumors expressed VISTA together with IDO. Patients featuring tumors with high numbers of IDO-positive TILs had better patient survival (<i>p</i> = 0.037). VISTA, LAG3, and TIM3 expression did not correlate with survival. The analysis of publicly available data did not show survival differences. Tumors rarely co-express more than two immune molecules at the same time, and VISTA is most frequently co-expressed. Although IDO generally inhibits T-cell proliferation, a high expression of IDO was associated with improved survival. We expect immune checkpoint inhibitors against VISTA, LAG3, and TIM3 to be inefficient in a clinical application.https://www.mdpi.com/2072-6694/13/11/2689pancreatic cancerimmune checkpointimmune moleculestumor-infiltrating lymphocytesIDOVISTA
collection DOAJ
language English
format Article
sources DOAJ
author Felix C. Popp
Ingracia Capino
Joana Bartels
Alexander Damanakis
Jiahui Li
Rabi R. Datta
Heike Löser
Yue Zhao
Alexander Quaas
Philipp Lohneis
Christiane J. Bruns
on behalf of the PANCALYZE Study Group
spellingShingle Felix C. Popp
Ingracia Capino
Joana Bartels
Alexander Damanakis
Jiahui Li
Rabi R. Datta
Heike Löser
Yue Zhao
Alexander Quaas
Philipp Lohneis
Christiane J. Bruns
on behalf of the PANCALYZE Study Group
Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma
Cancers
pancreatic cancer
immune checkpoint
immune molecules
tumor-infiltrating lymphocytes
IDO
VISTA
author_facet Felix C. Popp
Ingracia Capino
Joana Bartels
Alexander Damanakis
Jiahui Li
Rabi R. Datta
Heike Löser
Yue Zhao
Alexander Quaas
Philipp Lohneis
Christiane J. Bruns
on behalf of the PANCALYZE Study Group
author_sort Felix C. Popp
title Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma
title_short Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma
title_full Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma
title_fullStr Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma
title_full_unstemmed Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma
title_sort expression of immune checkpoint regulators ido, vista, lag3, and tim3 in resected pancreatic ductal adenocarcinoma
publisher MDPI AG
series Cancers
issn 2072-6694
publishDate 2021-05-01
description Pancreatic cancer features elaborate mechanisms of immune evasion. The potential of new immune molecules was explored to restore the antitumor immune response. If these immune molecules are associated with poor survival, specific drugs could take effect. Here, we analyze the expression of VISTA, LAG3, IDO, and TIM3 on tumor-infiltrating lymphocytes (TILs) and its impact on patient survival. We analyzed 153 pancreatic cancer patients from the prospectively managed database of the multicentered PANCALYZE study. Immunohistochemistry on a tissue microarray assessed VISTA, LAG3, IDO, and TIM3 expression of TILs from the patients undergoing primary resection. Complementarily, we analyzed publicly available transcriptomic data (<i>n</i> = 903). Successful completion of chemotherapy, and lymph node status were independent predictors of survival in the multivariate analysis of the clinicopathologic parameters. Fifteen tumors were exclusively VISTA-positive, thirteen tumors expressed VISTA together with TIM3, and ten tumors expressed VISTA together with IDO. Patients featuring tumors with high numbers of IDO-positive TILs had better patient survival (<i>p</i> = 0.037). VISTA, LAG3, and TIM3 expression did not correlate with survival. The analysis of publicly available data did not show survival differences. Tumors rarely co-express more than two immune molecules at the same time, and VISTA is most frequently co-expressed. Although IDO generally inhibits T-cell proliferation, a high expression of IDO was associated with improved survival. We expect immune checkpoint inhibitors against VISTA, LAG3, and TIM3 to be inefficient in a clinical application.
topic pancreatic cancer
immune checkpoint
immune molecules
tumor-infiltrating lymphocytes
IDO
VISTA
url https://www.mdpi.com/2072-6694/13/11/2689
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