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Resistance of MMTV-NeuT/ATTAC mice to anti-PD-1 immune checkpoint therapy is associated with macrophage infiltration and Wnt pathway expression
One of the central challenges for cancer therapy is the identification of factors in the tumor microenvironment that increase tumor progression and immune tolerance. In breast cancer, fibrosis is a histopathologic criterion for invasive cancer and poor survival that results from inflammatory factors...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9765860/ https://www.ncbi.nlm.nih.gov/pubmed/36537914 http://dx.doi.org/10.18632/oncotarget.28330 |
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author | Yuan, Hongyan Jin, Lu Xiang, Handan Bhattacharya, Anannya Brandish, Philip E. Baltus, Gretchen Tong, Alexander Zhou, Changyan Glazer, Robert I. |
author_facet | Yuan, Hongyan Jin, Lu Xiang, Handan Bhattacharya, Anannya Brandish, Philip E. Baltus, Gretchen Tong, Alexander Zhou, Changyan Glazer, Robert I. |
author_sort | Yuan, Hongyan |
collection | PubMed |
description | One of the central challenges for cancer therapy is the identification of factors in the tumor microenvironment that increase tumor progression and immune tolerance. In breast cancer, fibrosis is a histopathologic criterion for invasive cancer and poor survival that results from inflammatory factors and remodeling of the extracellular matrix to produce an immune tolerant microenvironment. To determine whether tolerance is associated with the immune checkpoint, Programmed Cell Death 1 (PD-1), NeuT/ATTAC mice, a conditional model of mammary fibrosis that we recently developed, were administered a murine-specific anti-PD-1 mAb related to pembrolizumab, and drug response was monitored by tumor development, imaging mass cytometry, immunohistochemistry and tumor gene expression by RNAseq. Tumor progression in NeuT/ATTAC mice was unaffected by weekly injection of anti-PD-1 over four months. Insensitivity to anti-PD-1 was associated with several processes, including increased tumor-associated macrophages (TAM), epithelial to mesenchymal transition (EMT), fibroblast proliferation, an enhanced extracellular matrix and the Wnt signaling pathway, including increased expression of Fzd5, Wnt5a, Vimentin, Mmp3, Col2a1 and Tgfβ1. These results suggest potential therapeutic avenues that may enhance PD-1 immune checkpoint sensitivity, including the use of tumor microenvironment targeted agents and Wnt pathway inhibitors. |
format | Online Article Text |
id | pubmed-9765860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-97658602022-12-20 Resistance of MMTV-NeuT/ATTAC mice to anti-PD-1 immune checkpoint therapy is associated with macrophage infiltration and Wnt pathway expression Yuan, Hongyan Jin, Lu Xiang, Handan Bhattacharya, Anannya Brandish, Philip E. Baltus, Gretchen Tong, Alexander Zhou, Changyan Glazer, Robert I. Oncotarget Research Paper One of the central challenges for cancer therapy is the identification of factors in the tumor microenvironment that increase tumor progression and immune tolerance. In breast cancer, fibrosis is a histopathologic criterion for invasive cancer and poor survival that results from inflammatory factors and remodeling of the extracellular matrix to produce an immune tolerant microenvironment. To determine whether tolerance is associated with the immune checkpoint, Programmed Cell Death 1 (PD-1), NeuT/ATTAC mice, a conditional model of mammary fibrosis that we recently developed, were administered a murine-specific anti-PD-1 mAb related to pembrolizumab, and drug response was monitored by tumor development, imaging mass cytometry, immunohistochemistry and tumor gene expression by RNAseq. Tumor progression in NeuT/ATTAC mice was unaffected by weekly injection of anti-PD-1 over four months. Insensitivity to anti-PD-1 was associated with several processes, including increased tumor-associated macrophages (TAM), epithelial to mesenchymal transition (EMT), fibroblast proliferation, an enhanced extracellular matrix and the Wnt signaling pathway, including increased expression of Fzd5, Wnt5a, Vimentin, Mmp3, Col2a1 and Tgfβ1. These results suggest potential therapeutic avenues that may enhance PD-1 immune checkpoint sensitivity, including the use of tumor microenvironment targeted agents and Wnt pathway inhibitors. Impact Journals LLC 2022-12-20 /pmc/articles/PMC9765860/ /pubmed/36537914 http://dx.doi.org/10.18632/oncotarget.28330 Text en Copyright: © 2022 Yuan et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Yuan, Hongyan Jin, Lu Xiang, Handan Bhattacharya, Anannya Brandish, Philip E. Baltus, Gretchen Tong, Alexander Zhou, Changyan Glazer, Robert I. Resistance of MMTV-NeuT/ATTAC mice to anti-PD-1 immune checkpoint therapy is associated with macrophage infiltration and Wnt pathway expression |
title | Resistance of MMTV-NeuT/ATTAC mice to anti-PD-1 immune checkpoint therapy is associated with macrophage infiltration and Wnt pathway expression |
title_full | Resistance of MMTV-NeuT/ATTAC mice to anti-PD-1 immune checkpoint therapy is associated with macrophage infiltration and Wnt pathway expression |
title_fullStr | Resistance of MMTV-NeuT/ATTAC mice to anti-PD-1 immune checkpoint therapy is associated with macrophage infiltration and Wnt pathway expression |
title_full_unstemmed | Resistance of MMTV-NeuT/ATTAC mice to anti-PD-1 immune checkpoint therapy is associated with macrophage infiltration and Wnt pathway expression |
title_short | Resistance of MMTV-NeuT/ATTAC mice to anti-PD-1 immune checkpoint therapy is associated with macrophage infiltration and Wnt pathway expression |
title_sort | resistance of mmtv-neut/attac mice to anti-pd-1 immune checkpoint therapy is associated with macrophage infiltration and wnt pathway expression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9765860/ https://www.ncbi.nlm.nih.gov/pubmed/36537914 http://dx.doi.org/10.18632/oncotarget.28330 |
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