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Unveiling the Link Between Inflammation and Adaptive Immunity in Breast Cancer
Inflammation has been recognized as an important driver in the development and growth of malignancies. Inflammatory signaling in cancer emerges from the combinatorial interaction of several deregulated pathways. Pathway deregulation is often driven by changes in the underlying gene regulatory networ...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362261/ https://www.ncbi.nlm.nih.gov/pubmed/30761130 http://dx.doi.org/10.3389/fimmu.2019.00056 |
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author | Velazquez-Caldelas, Tadeo Enrique Alcalá-Corona, Sergio Antonio Espinal-Enríquez, Jesús Hernandez-Lemus, Enrique |
author_facet | Velazquez-Caldelas, Tadeo Enrique Alcalá-Corona, Sergio Antonio Espinal-Enríquez, Jesús Hernandez-Lemus, Enrique |
author_sort | Velazquez-Caldelas, Tadeo Enrique |
collection | PubMed |
description | Inflammation has been recognized as an important driver in the development and growth of malignancies. Inflammatory signaling in cancer emerges from the combinatorial interaction of several deregulated pathways. Pathway deregulation is often driven by changes in the underlying gene regulatory networks. Confronted with such complex scenario, it can be argued that a closer analysis of the structure of such regulatory networks will shed some light on how gene deregulation led to sustained inflammation in cancer. Here, we inferred an inflammation-associated gene regulatory network from 641 breast cancer and 78 healthy samples. A modular structure analysis of the regulatory network was carried out, revealing a hierarchical modular structure. Modules show significant overrepresentation score p-values for biological processes unveiling a definite association between inflammatory processes and adaptive immunity. Other modules are enriched for T-cell activation, differentiation of CD8(+) lymphocytes and immune cell migration, thus reinforcing the aforementioned association. These analyses suggest that in breast cancer tumors, the balance between antitumor response and immune tolerance involving CD8(+) T cells is tipped in favor of the tumor. One possible mechanism is the induction of tolerance and anergization of these cells by persistent antigen exposure. |
format | Online Article Text |
id | pubmed-6362261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63622612019-02-13 Unveiling the Link Between Inflammation and Adaptive Immunity in Breast Cancer Velazquez-Caldelas, Tadeo Enrique Alcalá-Corona, Sergio Antonio Espinal-Enríquez, Jesús Hernandez-Lemus, Enrique Front Immunol Immunology Inflammation has been recognized as an important driver in the development and growth of malignancies. Inflammatory signaling in cancer emerges from the combinatorial interaction of several deregulated pathways. Pathway deregulation is often driven by changes in the underlying gene regulatory networks. Confronted with such complex scenario, it can be argued that a closer analysis of the structure of such regulatory networks will shed some light on how gene deregulation led to sustained inflammation in cancer. Here, we inferred an inflammation-associated gene regulatory network from 641 breast cancer and 78 healthy samples. A modular structure analysis of the regulatory network was carried out, revealing a hierarchical modular structure. Modules show significant overrepresentation score p-values for biological processes unveiling a definite association between inflammatory processes and adaptive immunity. Other modules are enriched for T-cell activation, differentiation of CD8(+) lymphocytes and immune cell migration, thus reinforcing the aforementioned association. These analyses suggest that in breast cancer tumors, the balance between antitumor response and immune tolerance involving CD8(+) T cells is tipped in favor of the tumor. One possible mechanism is the induction of tolerance and anergization of these cells by persistent antigen exposure. Frontiers Media S.A. 2019-01-29 /pmc/articles/PMC6362261/ /pubmed/30761130 http://dx.doi.org/10.3389/fimmu.2019.00056 Text en Copyright © 2019 Velazquez-Caldelas, Alcalá-Corona, Espinal-Enríquez and Hernandez-Lemus. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Velazquez-Caldelas, Tadeo Enrique Alcalá-Corona, Sergio Antonio Espinal-Enríquez, Jesús Hernandez-Lemus, Enrique Unveiling the Link Between Inflammation and Adaptive Immunity in Breast Cancer |
title | Unveiling the Link Between Inflammation and Adaptive Immunity in Breast Cancer |
title_full | Unveiling the Link Between Inflammation and Adaptive Immunity in Breast Cancer |
title_fullStr | Unveiling the Link Between Inflammation and Adaptive Immunity in Breast Cancer |
title_full_unstemmed | Unveiling the Link Between Inflammation and Adaptive Immunity in Breast Cancer |
title_short | Unveiling the Link Between Inflammation and Adaptive Immunity in Breast Cancer |
title_sort | unveiling the link between inflammation and adaptive immunity in breast cancer |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362261/ https://www.ncbi.nlm.nih.gov/pubmed/30761130 http://dx.doi.org/10.3389/fimmu.2019.00056 |
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