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The Prognostic Implications of Macrophages Expressing Proliferating Cell Nuclear Antigen in Breast Cancer Depend on Immune Context
Tumor associated macrophages (TAMs) are recruited from the circulation to the tumor site, and can undergo a spectrum of phenotypic changes, with two contrasting activation states described in the literature: the M1 and M2 phenotypes. We previously identified a population of TAMs that express prolife...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812150/ https://www.ncbi.nlm.nih.gov/pubmed/24205370 http://dx.doi.org/10.1371/journal.pone.0079114 |
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author | Campbell, Michael J. Wolf, Denise Mukhtar, Rita A. Tandon, Vickram Yau, Christina Au, Alfred Baehner, Frederick van’t Veer, Laura Berry, Donald Esserman, Laura J. |
author_facet | Campbell, Michael J. Wolf, Denise Mukhtar, Rita A. Tandon, Vickram Yau, Christina Au, Alfred Baehner, Frederick van’t Veer, Laura Berry, Donald Esserman, Laura J. |
author_sort | Campbell, Michael J. |
collection | PubMed |
description | Tumor associated macrophages (TAMs) are recruited from the circulation to the tumor site, and can undergo a spectrum of phenotypic changes, with two contrasting activation states described in the literature: the M1 and M2 phenotypes. We previously identified a population of TAMs that express proliferating cell nuclear antigen (PCNA) and are associated with high grade, hormone receptor negative breast cancers and poor outcomes. In the present exploratory study we again found that high PCNA(+) TAM counts in pre-treatment tumor biopsies (102 invasive breast cancer cases from the I-SPY 1 Trial, a prospective neoadjuvant trial with serial core biopsies and gene array data) were associated with high grade, hormone receptor negativity, and decreased recurrence free survival. We explored the association of these PCNA(+) TAMs with the expression of M1 and M2 related genes and, contrary to expectation, observed that high PCNA(+) TAM levels were associated with more M1- than M2-related genes. An immune gene signature, derived from cytotoxic T cell and MHC Class II genes (Tc/ClassII), was developed and we found that high PCNA(+) TAM counts, in the context of a low Tc/ClassII signature score, were associated with significantly worse recurrence free survival in all cases and in hormone receptor negative only cases. We observed similar results using a gene signature-proxy for PCNA(+) TAMs in a larger independent set of 425 neoadjuvant-treated breast cancer cases. The results of this exploratory study indicate that high numbers of PCNA(+) TAMs, in the absence of an anti-tumor immune microenvironment (as indicated by a low Tc/ClassII signature score), are associated with poor outcomes in breast cancer patients treated with neoadjuvant chemotherapy. This, along with the observation that PCNA(+) TAMs were associated predominantly with M1-related genes, may provide new insights into the role of the immune microenvironment in breast cancer. |
format | Online Article Text |
id | pubmed-3812150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38121502013-11-07 The Prognostic Implications of Macrophages Expressing Proliferating Cell Nuclear Antigen in Breast Cancer Depend on Immune Context Campbell, Michael J. Wolf, Denise Mukhtar, Rita A. Tandon, Vickram Yau, Christina Au, Alfred Baehner, Frederick van’t Veer, Laura Berry, Donald Esserman, Laura J. PLoS One Research Article Tumor associated macrophages (TAMs) are recruited from the circulation to the tumor site, and can undergo a spectrum of phenotypic changes, with two contrasting activation states described in the literature: the M1 and M2 phenotypes. We previously identified a population of TAMs that express proliferating cell nuclear antigen (PCNA) and are associated with high grade, hormone receptor negative breast cancers and poor outcomes. In the present exploratory study we again found that high PCNA(+) TAM counts in pre-treatment tumor biopsies (102 invasive breast cancer cases from the I-SPY 1 Trial, a prospective neoadjuvant trial with serial core biopsies and gene array data) were associated with high grade, hormone receptor negativity, and decreased recurrence free survival. We explored the association of these PCNA(+) TAMs with the expression of M1 and M2 related genes and, contrary to expectation, observed that high PCNA(+) TAM levels were associated with more M1- than M2-related genes. An immune gene signature, derived from cytotoxic T cell and MHC Class II genes (Tc/ClassII), was developed and we found that high PCNA(+) TAM counts, in the context of a low Tc/ClassII signature score, were associated with significantly worse recurrence free survival in all cases and in hormone receptor negative only cases. We observed similar results using a gene signature-proxy for PCNA(+) TAMs in a larger independent set of 425 neoadjuvant-treated breast cancer cases. The results of this exploratory study indicate that high numbers of PCNA(+) TAMs, in the absence of an anti-tumor immune microenvironment (as indicated by a low Tc/ClassII signature score), are associated with poor outcomes in breast cancer patients treated with neoadjuvant chemotherapy. This, along with the observation that PCNA(+) TAMs were associated predominantly with M1-related genes, may provide new insights into the role of the immune microenvironment in breast cancer. Public Library of Science 2013-10-29 /pmc/articles/PMC3812150/ /pubmed/24205370 http://dx.doi.org/10.1371/journal.pone.0079114 Text en © 2013 Campbell et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Campbell, Michael J. Wolf, Denise Mukhtar, Rita A. Tandon, Vickram Yau, Christina Au, Alfred Baehner, Frederick van’t Veer, Laura Berry, Donald Esserman, Laura J. The Prognostic Implications of Macrophages Expressing Proliferating Cell Nuclear Antigen in Breast Cancer Depend on Immune Context |
title | The Prognostic Implications of Macrophages Expressing Proliferating Cell Nuclear Antigen in Breast Cancer Depend on Immune Context |
title_full | The Prognostic Implications of Macrophages Expressing Proliferating Cell Nuclear Antigen in Breast Cancer Depend on Immune Context |
title_fullStr | The Prognostic Implications of Macrophages Expressing Proliferating Cell Nuclear Antigen in Breast Cancer Depend on Immune Context |
title_full_unstemmed | The Prognostic Implications of Macrophages Expressing Proliferating Cell Nuclear Antigen in Breast Cancer Depend on Immune Context |
title_short | The Prognostic Implications of Macrophages Expressing Proliferating Cell Nuclear Antigen in Breast Cancer Depend on Immune Context |
title_sort | prognostic implications of macrophages expressing proliferating cell nuclear antigen in breast cancer depend on immune context |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812150/ https://www.ncbi.nlm.nih.gov/pubmed/24205370 http://dx.doi.org/10.1371/journal.pone.0079114 |
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