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Regulatory T Cells in Pancreatic Cancer: Of Mice and Men
SIMPLE SUMMARY: Regulatory T cells (Treg) are a major immunosuppressive cell subset in the pancreatic tumor microenvironment. Tregs influence tumor growth by acting either directly on cancer cells or via the inhibition of effector immune cells. Treg cells form a partially redundant network with othe...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559359/ https://www.ncbi.nlm.nih.gov/pubmed/36230505 http://dx.doi.org/10.3390/cancers14194582 |
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author | Mota Reyes, Carmen Demir, Elke Çifcibaşı, Kaan Istvanffy, Rouzanna Friess, Helmut Demir, Ihsan Ekin |
author_facet | Mota Reyes, Carmen Demir, Elke Çifcibaşı, Kaan Istvanffy, Rouzanna Friess, Helmut Demir, Ihsan Ekin |
author_sort | Mota Reyes, Carmen |
collection | PubMed |
description | SIMPLE SUMMARY: Regulatory T cells (Treg) are a major immunosuppressive cell subset in the pancreatic tumor microenvironment. Tregs influence tumor growth by acting either directly on cancer cells or via the inhibition of effector immune cells. Treg cells form a partially redundant network with other immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) that confer robustness to tumor immunosuppression and resistance to immunotherapy. The results obtained in preclinical studies, whereupon Treg depletion, MDSCs concomitantly decreased in early tumors whereas an inverse association was seen in advanced PCa, urge a comprehensive analysis of the immunosuppressive profile of PCa throughout tumorigenesis. One relevant context to analyse these compensatory mechanisms may be patients with locally advanced PCa undergoing neoadjuvant therapy (neoTx). In order to understand these dynamics and to uncover stage-specific actional strategies involving Tregs, pre-clinical models that allow the administration of neoTx to different stages of PCa may be a very useful platform. ABSTRACT: Regulatory T cells (Treg) are one of the major immunosuppressive cell subsets in the pancreatic tumor microenvironment. Tregs influence tumor growth by acting either directly on cancer cells or via the inhibition of effector immune cells. Treg cells mechanisms form a partially redundant network with other immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) that confer robustness to tumor immunosuppression and resistance to immunotherapy. The results obtained in preclinical studies where after Treg depletion, MDSCs concomitantly decreased in early tumors whereas an inverse association was seen in advanced PCa, urge a comprehensive analysis of the immunosuppressive profile of PCa throughout tumorigenesis. One relevant context to analyse these complex compensatory mechanisms may be the tumors of patients who underwent neoTx. Here, we observed a parallel decrease in the numbers of both intratumoral Tregs and MDSC after neoTx even in locally advanced PCa. NeoTx also led to decreased amounts of αSMA(+) myofibroblastic cancer-associated fibroblasts (myCAF) and increased proportions of CD8(+) cytotoxic T lymphocytes in the tumor. In order to understand these dynamics and to uncover stage-specific actional strategies involving Tregs, pre-clinical models that allow the administration of neoTx to different stages of PCa may be a very useful platform. |
format | Online Article Text |
id | pubmed-9559359 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95593592022-10-14 Regulatory T Cells in Pancreatic Cancer: Of Mice and Men Mota Reyes, Carmen Demir, Elke Çifcibaşı, Kaan Istvanffy, Rouzanna Friess, Helmut Demir, Ihsan Ekin Cancers (Basel) Communication SIMPLE SUMMARY: Regulatory T cells (Treg) are a major immunosuppressive cell subset in the pancreatic tumor microenvironment. Tregs influence tumor growth by acting either directly on cancer cells or via the inhibition of effector immune cells. Treg cells form a partially redundant network with other immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) that confer robustness to tumor immunosuppression and resistance to immunotherapy. The results obtained in preclinical studies, whereupon Treg depletion, MDSCs concomitantly decreased in early tumors whereas an inverse association was seen in advanced PCa, urge a comprehensive analysis of the immunosuppressive profile of PCa throughout tumorigenesis. One relevant context to analyse these compensatory mechanisms may be patients with locally advanced PCa undergoing neoadjuvant therapy (neoTx). In order to understand these dynamics and to uncover stage-specific actional strategies involving Tregs, pre-clinical models that allow the administration of neoTx to different stages of PCa may be a very useful platform. ABSTRACT: Regulatory T cells (Treg) are one of the major immunosuppressive cell subsets in the pancreatic tumor microenvironment. Tregs influence tumor growth by acting either directly on cancer cells or via the inhibition of effector immune cells. Treg cells mechanisms form a partially redundant network with other immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) that confer robustness to tumor immunosuppression and resistance to immunotherapy. The results obtained in preclinical studies where after Treg depletion, MDSCs concomitantly decreased in early tumors whereas an inverse association was seen in advanced PCa, urge a comprehensive analysis of the immunosuppressive profile of PCa throughout tumorigenesis. One relevant context to analyse these complex compensatory mechanisms may be the tumors of patients who underwent neoTx. Here, we observed a parallel decrease in the numbers of both intratumoral Tregs and MDSC after neoTx even in locally advanced PCa. NeoTx also led to decreased amounts of αSMA(+) myofibroblastic cancer-associated fibroblasts (myCAF) and increased proportions of CD8(+) cytotoxic T lymphocytes in the tumor. In order to understand these dynamics and to uncover stage-specific actional strategies involving Tregs, pre-clinical models that allow the administration of neoTx to different stages of PCa may be a very useful platform. MDPI 2022-09-21 /pmc/articles/PMC9559359/ /pubmed/36230505 http://dx.doi.org/10.3390/cancers14194582 Text en © 2022 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 | Communication Mota Reyes, Carmen Demir, Elke Çifcibaşı, Kaan Istvanffy, Rouzanna Friess, Helmut Demir, Ihsan Ekin Regulatory T Cells in Pancreatic Cancer: Of Mice and Men |
title | Regulatory T Cells in Pancreatic Cancer: Of Mice and Men |
title_full | Regulatory T Cells in Pancreatic Cancer: Of Mice and Men |
title_fullStr | Regulatory T Cells in Pancreatic Cancer: Of Mice and Men |
title_full_unstemmed | Regulatory T Cells in Pancreatic Cancer: Of Mice and Men |
title_short | Regulatory T Cells in Pancreatic Cancer: Of Mice and Men |
title_sort | regulatory t cells in pancreatic cancer: of mice and men |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559359/ https://www.ncbi.nlm.nih.gov/pubmed/36230505 http://dx.doi.org/10.3390/cancers14194582 |
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