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The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling
BACKGROUND: The characterization of the immune component of the tumor microenvironment (TME) of human epidermal growth factor receptor 2 positive (HER2+) breast cancer has been limited. Molecular and spatial characterization of HER2+ TME of primary, recurrent, and metastatic breast tumors has the po...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626906/ https://www.ncbi.nlm.nih.gov/pubmed/34838031 http://dx.doi.org/10.1186/s12967-021-03113-9 |
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author | Schlam, Ilana Church, Sarah E. Hether, Tyler D. Chaldekas, Krysta Hudson, Briana M. White, Andrew M. Maisonet, Emily Harris, Brent T. Swain, Sandra M. |
author_facet | Schlam, Ilana Church, Sarah E. Hether, Tyler D. Chaldekas, Krysta Hudson, Briana M. White, Andrew M. Maisonet, Emily Harris, Brent T. Swain, Sandra M. |
author_sort | Schlam, Ilana |
collection | PubMed |
description | BACKGROUND: The characterization of the immune component of the tumor microenvironment (TME) of human epidermal growth factor receptor 2 positive (HER2+) breast cancer has been limited. Molecular and spatial characterization of HER2+ TME of primary, recurrent, and metastatic breast tumors has the potential to identify immune mediated mechanisms and biomarker targets that could be used to guide selection of therapies. METHODS: We examined 15 specimens from eight patients with HER2+ breast cancer: 10 primary breast tumors (PBT), two soft tissue, one lung, and two brain metastases (BM). Using molecular profiling by bulk gene expression TME signatures, including the Tumor Inflammation Signature (TIS) and PAM50 subtyping, as well as spatial characterization of immune hot, warm, and cold regions in the stroma and tumor epithelium using 64 protein targets on the GeoMx Digital Spatial Profiler. RESULTS: PBT had higher infiltration of immune cells relative to metastatic sites and higher protein and gene expression of immune activation markers when compared to metastatic sites. TIS scores were lower in metastases, particularly in BM. BM also had less immune infiltration overall, but in the stromal compartment with the highest density of immune infiltration had similar levels of T cells that were less activated than PBT stromal regions suggesting immune exclusion in the tumor epithelium. CONCLUSIONS: Our findings show stromal and tumor localized immune cells in the TME are more active in primary versus metastatic disease. This suggests patients with early HER2+ breast cancer could have more benefit from immune-targeting therapies than patients with advanced disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-03113-9. |
format | Online Article Text |
id | pubmed-8626906 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86269062021-11-29 The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling Schlam, Ilana Church, Sarah E. Hether, Tyler D. Chaldekas, Krysta Hudson, Briana M. White, Andrew M. Maisonet, Emily Harris, Brent T. Swain, Sandra M. J Transl Med Research BACKGROUND: The characterization of the immune component of the tumor microenvironment (TME) of human epidermal growth factor receptor 2 positive (HER2+) breast cancer has been limited. Molecular and spatial characterization of HER2+ TME of primary, recurrent, and metastatic breast tumors has the potential to identify immune mediated mechanisms and biomarker targets that could be used to guide selection of therapies. METHODS: We examined 15 specimens from eight patients with HER2+ breast cancer: 10 primary breast tumors (PBT), two soft tissue, one lung, and two brain metastases (BM). Using molecular profiling by bulk gene expression TME signatures, including the Tumor Inflammation Signature (TIS) and PAM50 subtyping, as well as spatial characterization of immune hot, warm, and cold regions in the stroma and tumor epithelium using 64 protein targets on the GeoMx Digital Spatial Profiler. RESULTS: PBT had higher infiltration of immune cells relative to metastatic sites and higher protein and gene expression of immune activation markers when compared to metastatic sites. TIS scores were lower in metastases, particularly in BM. BM also had less immune infiltration overall, but in the stromal compartment with the highest density of immune infiltration had similar levels of T cells that were less activated than PBT stromal regions suggesting immune exclusion in the tumor epithelium. CONCLUSIONS: Our findings show stromal and tumor localized immune cells in the TME are more active in primary versus metastatic disease. This suggests patients with early HER2+ breast cancer could have more benefit from immune-targeting therapies than patients with advanced disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-03113-9. BioMed Central 2021-11-27 /pmc/articles/PMC8626906/ /pubmed/34838031 http://dx.doi.org/10.1186/s12967-021-03113-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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 Schlam, Ilana Church, Sarah E. Hether, Tyler D. Chaldekas, Krysta Hudson, Briana M. White, Andrew M. Maisonet, Emily Harris, Brent T. Swain, Sandra M. The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling |
title | The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling |
title_full | The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling |
title_fullStr | The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling |
title_full_unstemmed | The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling |
title_short | The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling |
title_sort | tumor immune microenvironment of primary and metastatic her2− positive breast cancers utilizing gene expression and spatial proteomic profiling |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626906/ https://www.ncbi.nlm.nih.gov/pubmed/34838031 http://dx.doi.org/10.1186/s12967-021-03113-9 |
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