The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling

Abstract 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 ha...

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Autores principales:	Ilana Schlam, Sarah E. Church, Tyler D. Hether, Krysta Chaldekas, Briana M. Hudson, Andrew M. White, Emily Maisonet, Brent T. Harris, Sandra M. Swain
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Breast cancer HER2 positive Tumor microenvironment Digital spatial profiling Gene expression profiling Medicine R
Acceso en línea:	https://doaj.org/article/815f26c1bb0147c2a0736d6023a43c34
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spelling	oai:doaj.org-article:815f26c1bb0147c2a0736d6023a43c342021-11-28T12:06:42ZThe tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling10.1186/s12967-021-03113-91479-5876https://doaj.org/article/815f26c1bb0147c2a0736d6023a43c342021-11-01T00:00:00Zhttps://doi.org/10.1186/s12967-021-03113-9https://doaj.org/toc/1479-5876Abstract 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.Ilana SchlamSarah E. ChurchTyler D. HetherKrysta ChaldekasBriana M. HudsonAndrew M. WhiteEmily MaisonetBrent T. HarrisSandra M. SwainBMCarticleBreast cancerHER2 positiveTumor microenvironmentDigital spatial profilingGene expression profilingMedicineRENJournal of Translational Medicine, Vol 19, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Breast cancer HER2 positive Tumor microenvironment Digital spatial profiling Gene expression profiling Medicine R
spellingShingle	Breast cancer HER2 positive Tumor microenvironment Digital spatial profiling Gene expression profiling Medicine R Ilana Schlam Sarah E. Church Tyler D. Hether Krysta Chaldekas Briana M. Hudson Andrew M. White Emily Maisonet Brent T. Harris Sandra M. Swain The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling
description	Abstract 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.
format	article
author	Ilana Schlam Sarah E. Church Tyler D. Hether Krysta Chaldekas Briana M. Hudson Andrew M. White Emily Maisonet Brent T. Harris Sandra M. Swain
author_facet	Ilana Schlam Sarah E. Church Tyler D. Hether Krysta Chaldekas Briana M. Hudson Andrew M. White Emily Maisonet Brent T. Harris Sandra M. Swain
author_sort	Ilana Schlam
title	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_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_sort	tumor immune microenvironment of primary and metastatic her2− positive breast cancers utilizing gene expression and spatial proteomic profiling
publisher	BMC
publishDate	2021
url	https://doaj.org/article/815f26c1bb0147c2a0736d6023a43c34
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The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling

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