Cargando…

The Immune Checkpoint Landscape in Tumor Cells of Pancreatic Ductal Adenocarcinoma

Immune checkpoint therapy (ICT) has shown promising potential in the treatment of multiple solid tumors. However, the role of ICT in pancreatic ductal adenocarcinoma (PDAC) remains limited. Patterns of immune checkpoints (ICs) in PDAC represent the basis for establishing a potent ICT. The aim of thi...

Descripción completa

Detalles Bibliográficos
Autores principales: Loch, Florian N., Kamphues, Carsten, Beyer, Katharina, Schineis, Christian, Rayya, Wael, Lauscher, Johannes C., Horst, David, Dragomir, Mihnea P., Schallenberg, Simon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917344/
https://www.ncbi.nlm.nih.gov/pubmed/36768480
http://dx.doi.org/10.3390/ijms24032160
_version_ 1784886343169474560
author Loch, Florian N.
Kamphues, Carsten
Beyer, Katharina
Schineis, Christian
Rayya, Wael
Lauscher, Johannes C.
Horst, David
Dragomir, Mihnea P.
Schallenberg, Simon
author_facet Loch, Florian N.
Kamphues, Carsten
Beyer, Katharina
Schineis, Christian
Rayya, Wael
Lauscher, Johannes C.
Horst, David
Dragomir, Mihnea P.
Schallenberg, Simon
author_sort Loch, Florian N.
collection PubMed
description Immune checkpoint therapy (ICT) has shown promising potential in the treatment of multiple solid tumors. However, the role of ICT in pancreatic ductal adenocarcinoma (PDAC) remains limited. Patterns of immune checkpoints (ICs) in PDAC represent the basis for establishing a potent ICT. The aim of this study is to create a profile of IC expression and its prognostic relevance in cancer cells of PDAC. Therefore, tumor cells from peripheral and central tissue microarray (TMA) spots from histologically confirmed PDAC of 68 patients after tumor resection were investigated in terms of expressions of TIM3, IDO, B7H4, LAG3, VISTA, and PD-L1 using immunohistochemistry. The presence of the respective ICs was compared to overall survival (OS). The presence of VISTA and PD-L1 significantly correlates with shorter OS (median OS: 22 months vs. 7 months and 22 months vs. 11 months, respectively, p < 0.05). For the presence of TIM3, IDO, B7H4, and LAG3, no difference in OS was observed (p > 0.05). The analysis of OS of combined subgroups for VISTA and PD-L1 (VISTA and PD-L1 neg., VISTA pos. and PD-L1 neg., VISTA neg. and PD-L1 pos., and VISTA and PD-L1 pos.) yielded overall statistical significance difference (p = 0.02). These results suggest that the presence of VISTA and PD-L1 is of prognostic relevance and potentially qualifies them as targets for ICT.
format Online
Article
Text
id pubmed-9917344
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-99173442023-02-11 The Immune Checkpoint Landscape in Tumor Cells of Pancreatic Ductal Adenocarcinoma Loch, Florian N. Kamphues, Carsten Beyer, Katharina Schineis, Christian Rayya, Wael Lauscher, Johannes C. Horst, David Dragomir, Mihnea P. Schallenberg, Simon Int J Mol Sci Article Immune checkpoint therapy (ICT) has shown promising potential in the treatment of multiple solid tumors. However, the role of ICT in pancreatic ductal adenocarcinoma (PDAC) remains limited. Patterns of immune checkpoints (ICs) in PDAC represent the basis for establishing a potent ICT. The aim of this study is to create a profile of IC expression and its prognostic relevance in cancer cells of PDAC. Therefore, tumor cells from peripheral and central tissue microarray (TMA) spots from histologically confirmed PDAC of 68 patients after tumor resection were investigated in terms of expressions of TIM3, IDO, B7H4, LAG3, VISTA, and PD-L1 using immunohistochemistry. The presence of the respective ICs was compared to overall survival (OS). The presence of VISTA and PD-L1 significantly correlates with shorter OS (median OS: 22 months vs. 7 months and 22 months vs. 11 months, respectively, p < 0.05). For the presence of TIM3, IDO, B7H4, and LAG3, no difference in OS was observed (p > 0.05). The analysis of OS of combined subgroups for VISTA and PD-L1 (VISTA and PD-L1 neg., VISTA pos. and PD-L1 neg., VISTA neg. and PD-L1 pos., and VISTA and PD-L1 pos.) yielded overall statistical significance difference (p = 0.02). These results suggest that the presence of VISTA and PD-L1 is of prognostic relevance and potentially qualifies them as targets for ICT. MDPI 2023-01-21 /pmc/articles/PMC9917344/ /pubmed/36768480 http://dx.doi.org/10.3390/ijms24032160 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Loch, Florian N.
Kamphues, Carsten
Beyer, Katharina
Schineis, Christian
Rayya, Wael
Lauscher, Johannes C.
Horst, David
Dragomir, Mihnea P.
Schallenberg, Simon
The Immune Checkpoint Landscape in Tumor Cells of Pancreatic Ductal Adenocarcinoma
title The Immune Checkpoint Landscape in Tumor Cells of Pancreatic Ductal Adenocarcinoma
title_full The Immune Checkpoint Landscape in Tumor Cells of Pancreatic Ductal Adenocarcinoma
title_fullStr The Immune Checkpoint Landscape in Tumor Cells of Pancreatic Ductal Adenocarcinoma
title_full_unstemmed The Immune Checkpoint Landscape in Tumor Cells of Pancreatic Ductal Adenocarcinoma
title_short The Immune Checkpoint Landscape in Tumor Cells of Pancreatic Ductal Adenocarcinoma
title_sort immune checkpoint landscape in tumor cells of pancreatic ductal adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917344/
https://www.ncbi.nlm.nih.gov/pubmed/36768480
http://dx.doi.org/10.3390/ijms24032160
work_keys_str_mv AT lochfloriann theimmunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT kamphuescarsten theimmunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT beyerkatharina theimmunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT schineischristian theimmunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT rayyawael theimmunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT lauscherjohannesc theimmunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT horstdavid theimmunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT dragomirmihneap theimmunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT schallenbergsimon theimmunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT lochfloriann immunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT kamphuescarsten immunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT beyerkatharina immunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT schineischristian immunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT rayyawael immunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT lauscherjohannesc immunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT horstdavid immunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT dragomirmihneap immunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma
AT schallenbergsimon immunecheckpointlandscapeintumorcellsofpancreaticductaladenocarcinoma