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Immune phenotype of patients with stage IV metastatic inflammatory breast cancer
BACKGROUND: Inflammatory breast cancer (IBC) is a rare but aggressive carcinoma characterized by severe erythema and edema of the breast, with many patients presenting in advanced metastatic disease. The “inflammatory” nature is not due to classic immune-mediated inflammation, but instead results fr...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709446/ https://www.ncbi.nlm.nih.gov/pubmed/33267869 http://dx.doi.org/10.1186/s13058-020-01371-x |
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author | Fernandez, Sandra V. MacFarlane, Alexander W. Jillab, Mowafaq Arisi, Maria F. Yearley, Jennifer Annamalai, Lakshmanan Gong, Yulan Cai, Kathy Q. Alpaugh, R. Katherine Cristofanilli, Massimo Campbell, Kerry S. |
author_facet | Fernandez, Sandra V. MacFarlane, Alexander W. Jillab, Mowafaq Arisi, Maria F. Yearley, Jennifer Annamalai, Lakshmanan Gong, Yulan Cai, Kathy Q. Alpaugh, R. Katherine Cristofanilli, Massimo Campbell, Kerry S. |
author_sort | Fernandez, Sandra V. |
collection | PubMed |
description | BACKGROUND: Inflammatory breast cancer (IBC) is a rare but aggressive carcinoma characterized by severe erythema and edema of the breast, with many patients presenting in advanced metastatic disease. The “inflammatory” nature is not due to classic immune-mediated inflammation, but instead results from tumor-mediated blockage of dermal lymphatic ducts. Previous work has shown that expression of PD-L1 on tumor cells can suppress T cell activation in triple-negative (TN) non-IBC breast cancer. In the present work, we investigated immune parameters in peripheral blood of metastatic IBC patients to determine whether cellular components of the immune system are altered, thereby contributing to pathogenesis of the disease. These immune parameters were also compared to PD-1 and PD-L1 expression in IBC tumor biopsies. METHODS: Flow cytometry-based immune phenotyping was performed using fresh peripheral blood from 14 stage IV IBC patients and compared to 11 healthy age-similar control women. Immunohistochemistry for CD20, CD3, PD-1, and PD-L1 was performed on tumor biopsies of these metastatic IBC patients. RESULTS: IBC patients with Stage IV disease had lymphopenia with significant reductions in circulating T, B, and NK cells. Reductions were observed in all subsets of CD4(+) T cells, whereas reductions in CD8(+) T cells were more concentrated in memory subsets. Immature cytokine-producing CD56(bright) NK cells expressed higher levels of FcγRIIIa and cytolytic granule components, suggesting accelerated maturation to cytolytic CD56(dim) cells. Immunohistochemical analysis of tumor biopsies demonstrated moderate to high expression of PD-1 in 18.2% of patients and of PD-L1 in 36.4% of patients. Interestingly, a positive correlation was observed between co-expression levels of PD-L1 and PD-1 in tumor biopsies, and higher expression of PD-L1 in tumor biopsies correlated with higher expression of cytolytic granule components in blood CD4(+) T cells and CD56(dim) NK cells, and higher numbers of CD8(+) effector memory T cells in peripheral blood. PD-1 expression in tumor also correlated with increased infiltration of CD20(+) B cells in the tumor. CONCLUSIONS: Our results suggest that while lymphocyte populations are severely compromised in stage IV IBC patients, an immune response toward the tumor had occurred in some patients, providing biological rationale to evaluate PD-1/PD-L1 immunotherapies for IBC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-020-01371-x. |
format | Online Article Text |
id | pubmed-7709446 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-77094462020-12-03 Immune phenotype of patients with stage IV metastatic inflammatory breast cancer Fernandez, Sandra V. MacFarlane, Alexander W. Jillab, Mowafaq Arisi, Maria F. Yearley, Jennifer Annamalai, Lakshmanan Gong, Yulan Cai, Kathy Q. Alpaugh, R. Katherine Cristofanilli, Massimo Campbell, Kerry S. Breast Cancer Res Research Article BACKGROUND: Inflammatory breast cancer (IBC) is a rare but aggressive carcinoma characterized by severe erythema and edema of the breast, with many patients presenting in advanced metastatic disease. The “inflammatory” nature is not due to classic immune-mediated inflammation, but instead results from tumor-mediated blockage of dermal lymphatic ducts. Previous work has shown that expression of PD-L1 on tumor cells can suppress T cell activation in triple-negative (TN) non-IBC breast cancer. In the present work, we investigated immune parameters in peripheral blood of metastatic IBC patients to determine whether cellular components of the immune system are altered, thereby contributing to pathogenesis of the disease. These immune parameters were also compared to PD-1 and PD-L1 expression in IBC tumor biopsies. METHODS: Flow cytometry-based immune phenotyping was performed using fresh peripheral blood from 14 stage IV IBC patients and compared to 11 healthy age-similar control women. Immunohistochemistry for CD20, CD3, PD-1, and PD-L1 was performed on tumor biopsies of these metastatic IBC patients. RESULTS: IBC patients with Stage IV disease had lymphopenia with significant reductions in circulating T, B, and NK cells. Reductions were observed in all subsets of CD4(+) T cells, whereas reductions in CD8(+) T cells were more concentrated in memory subsets. Immature cytokine-producing CD56(bright) NK cells expressed higher levels of FcγRIIIa and cytolytic granule components, suggesting accelerated maturation to cytolytic CD56(dim) cells. Immunohistochemical analysis of tumor biopsies demonstrated moderate to high expression of PD-1 in 18.2% of patients and of PD-L1 in 36.4% of patients. Interestingly, a positive correlation was observed between co-expression levels of PD-L1 and PD-1 in tumor biopsies, and higher expression of PD-L1 in tumor biopsies correlated with higher expression of cytolytic granule components in blood CD4(+) T cells and CD56(dim) NK cells, and higher numbers of CD8(+) effector memory T cells in peripheral blood. PD-1 expression in tumor also correlated with increased infiltration of CD20(+) B cells in the tumor. CONCLUSIONS: Our results suggest that while lymphocyte populations are severely compromised in stage IV IBC patients, an immune response toward the tumor had occurred in some patients, providing biological rationale to evaluate PD-1/PD-L1 immunotherapies for IBC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-020-01371-x. BioMed Central 2020-12-02 2020 /pmc/articles/PMC7709446/ /pubmed/33267869 http://dx.doi.org/10.1186/s13058-020-01371-x Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Fernandez, Sandra V. MacFarlane, Alexander W. Jillab, Mowafaq Arisi, Maria F. Yearley, Jennifer Annamalai, Lakshmanan Gong, Yulan Cai, Kathy Q. Alpaugh, R. Katherine Cristofanilli, Massimo Campbell, Kerry S. Immune phenotype of patients with stage IV metastatic inflammatory breast cancer |
title | Immune phenotype of patients with stage IV metastatic inflammatory breast cancer |
title_full | Immune phenotype of patients with stage IV metastatic inflammatory breast cancer |
title_fullStr | Immune phenotype of patients with stage IV metastatic inflammatory breast cancer |
title_full_unstemmed | Immune phenotype of patients with stage IV metastatic inflammatory breast cancer |
title_short | Immune phenotype of patients with stage IV metastatic inflammatory breast cancer |
title_sort | immune phenotype of patients with stage iv metastatic inflammatory breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709446/ https://www.ncbi.nlm.nih.gov/pubmed/33267869 http://dx.doi.org/10.1186/s13058-020-01371-x |
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