Evidence map›Paper›PMID 34838031›Full record

ArticleJournal of translational medicine2021

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

Ilana Schlam, Sarah E Church, Tyler D Hether, Krysta Chaldekas, Briana M Hudson, Andrew M White, Emily Maisonet, Brent T Harris, Sandra M Swain

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.1field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 29 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Ilana SchlamDepartment of Hematology-Oncology, MedStar Washington Hospital Center, Washington, DC, USA.
Sarah E ChurchNanoString Technologies Inc., Seattle, WA, USA.
Tyler D HetherNanoString Technologies Inc., Seattle, WA, USA.
Krysta ChaldekasMedStar Georgetown University Hospital, 4000 Reservoir road NW, 120 Building D, Washington, DC, 20057, USA.
Briana M HudsonDepartment of Hematology and Oncology, Tufts Medical Center, 800 Washington St, 245, Boston, MA, 02111, USA.
Andrew M WhiteNanoString Technologies Inc., Seattle, WA, USA.
Emily MaisonetMedStar Georgetown University Hospital, 4000 Reservoir road NW, 120 Building D, Washington, DC, 20057, USA.
Brent T HarrisMedStar Georgetown University Hospital, 4000 Reservoir road NW, 120 Building D, Washington, DC, 20057, USA.
Sandra M SwainMedStar Georgetown University Hospital, 4000 Reservoir road NW, 120 Building D, Washington, DC, 20057, USA. sms248@georgetown.edu.ORCID 0000-0002-1320-3830
Georgetown University · USNanostring Technologies (United States) · USMedStar Washington Hospital Center · USTufts Medical Center · US

Funding

Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI STEPHEN W BYERS · 1990 to 2026
$71.5M
NCI NIH HHS grant P30 CA051008NCI NIH HHS P30 CA051008
6 · The paper itself

Abstract

backgroundThe 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.

methodsWe 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.

resultsPBT 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.

conclusionsOur 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.

Indexed as

Breast NeoplasmsErb-b2 Receptor Tyrosine KinasesFemaleHumansNeoplasm Recurrence, LocalProteomicsTranscriptomeTumor MicroenvironmentErb-b2 Receptor Tyrosine KinasesBreast cancerDigital spatial profilingGene expression profilingHER2 positiveTumor microenvironment

Identifiers

PMID34838031
PMCPMC8626906
OpenAlexW3174712003

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.