On April 8, 2021 NanoString Technologies, Inc. (NASDAQ: NSTG), a leading provider of life science tools for discovery and translational research, reported the highlights of spatial biology abstracts that will be presented at the 2021 meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper), which will be held virtually from April 10 – 15, 2021 (Press release, NanoString Technologies, APR 8, 2021, View Source [SID1234577746]).
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The GeoMx Digital Spatial Profiler (DSP) enables researchers to characterize tissue morphology to rapidly and quantitatively profile RNA and proteins. To date, NanoString and its collaborators have presented DSP data in dozens of abstracts at major scientific meetings and more than 45 peer-reviewed publications, demonstrating DSP’s utility to address a wide range of biological questions in formalin-fixed paraffin-embedded (FFPE) and frozen tissues. At AACR (Free AACR Whitepaper) 2021, eight abstracts that used GeoMx DSP will be presented during the poster session on Saturday, April 10.
Four of the eight abstracts will be presented by investigators from the GeoMx Breast Cancer Consortium (GBCC), an international network of breast cancer researchers. Their goal is to apply innovative approaches and decipher the spatial context of breast cancer to develop a comprehensive atlas and database of novel biomarkers for the disease.
GBCC Abstracts
Poster 2718: Digital spatial profiling in HER2 positive breast cancer: The road to precision medicine
In this work, the GeoMx DSP was used to profile 71 protein targets and gene expression profiling was done using NanoString’s nCounter PanCancer IO360 assay for primary and metastatic tissues from human epidermal growth factor 2 positive (HER2+) breast cancer (BC) patients. A detailed characterization of carefully chosen immune cold, warm and hot regions of interest (ROI) in the tumor and tumor immune microenvironment of (HER2+) of these samples established that primary tumors had a higher number of immune cells than the metastatic sites. These findings, therefore, suggest that immunotherapy in early-stage BC could be more effective than in advanced BC.
Poster 2701: Molecular profiling to assess the immune response to neoadjuvant SABR in early breast cancer
NanoString’s Human PanCancer immune profiling panel was used to assess the impact of localized radiotherapy to elicit an immune response in primary breast carcinomas before lumpectomy. They analyzed 25 patient samples for low-risk primary breast carcinomas from the SIGNAL 2.0 clinical trial using the GeoMx DSP platform, pre, and post stereotactic body radiation therapy (SBRT). Significant differences were found in the gene expression patterns in the immune microenvironment gene expression patterns and cellular composition after radiotherapy, demonstrating that SBRT treatment indeed evokes an immune response, increasing the innate immune response.
Poster 2698: Spatial gene expression profiling in breast cancer
Transcriptome profiling was performed for a cohort of breast cancer lumpectomies using the Cancer Transcriptomic Atlas (CTA) assay on the GeoMx DSP platform. Analysis of 60 patient samples revealed region-specific heterogeneity in unifocal and multifocal cancer tumors. This study demonstrates and establishes the importance of interactions between immune and tumor cells in the tumor microenvironment and the need to develop a strategy to stratify patients to available targeted therapies.
Poster 2726: Characterization of immune microenvironment and heterogeneity in breast cancer subtypes
In this work, the immune microenvironment of Luminal A, Luminal B, Basal, and HER2 tumor subtypes in a cohort of early breast cancer patients was studied using protein biomarkers. The markers were delineated in a spatial context using the GeoMx DSP. Characterization of the immune microenvironment subtypes provided evidence for potential clinical use for GeoMx DSP in diagnosing and better stratifying breast cancer patients based on spatial heterogeneity in tumor and tumor microenvironment.
Other spatial abstracts
Poster 339: Resistance to trastuzumab is associated with alpha-smooth muscle actin expression in the stroma of patients with HER2+ breast cancer
GeoMx DSP was used to identify biomarkers for resistance to trastuzumab in HER2+ breast cancer. Fifty-eight protein targets were analyzed in three different regions of interest (tumor [PanCK+], leukocyte [CD45+/CD68-], and macrophage [CD68+]) in a cohort of 151 breast cancer patients that received trastuzumab. The study uncovered a-SMA as a potential biomarker to augment the predictive value of the current standard of care HER2 assay and justifies its further validation in the light of the many new HER2 targeted therapies.
Poster 705: SARS-CoV-2 infection of the human heart governs intracardiac innate immune response
Spatial profiling of human post-mortem cardiac samples of SARS-CoV-2 infected myocardium was carried out using NanoString’s Whole Transcriptome Analysis (1,864 genes) panel, along with a matching proteome panel on the GeoMx digital spatial profiler. The purpose of their investigation was to elucidate the molecular mechanisms underlying cardiac toxicity, a severe cause of morbidity and mortality in patients on DOX therapy. The study showed interesting gender-specific differential gene expression patterns in the myocardium between SARS-CoV-2 infected and control regions of interest. Signatures of enhanced innate and acquired immune signaling, apoptosis and autophagy, chromatin remodeling, reduced DNA repair, and reduced oxidoreductase activity were all observed in regions of infection. Additionally, DOX-induced increase in the expression of TMPSS2 and cathepsins A, B, and F, clearly indicated enhanced SARS-CoV-2 susceptibility in the myocardium, thus placing cancer patients on DOX therapy at increased risk of cardiac damage.
Poster 2731: Cell-type deconvolution of African American breast tumors reveals spatial heterogeneity of the immune microenvironment
Researchers at the University of Chicago carried out spatial gene expression analysis within localized segments of TNBC tumors from a cohort of self-reported African American patients in the Chicago Multi-Ethnic Breast Cancer Study (ChiMEC). Regions of interest for spatial characterization of tumor and tumor microenvironment using the GeoMx DSP Cancer Transcriptome Atlas assay were manually selected based on the specific morphologies. The 1,825 genes interrogated in the CTA assay provided a granular understanding of the immune landscape’s heterogeneity within tumors.
Poster 2771: Comprehensive analysis of immuno oncology markers in the tumor microenvironment of solid tumor samples using GeoMxTM digital spatial profiler (DSP) and MultiOmyxTM hyperplexed immunofluorescence (IF)
This study describes a multi-faceted highly multiplexed tissue analysis of critical Immuno oncology (IO) protein markers in a pan-cancer cohort of up to 35 FFPE samples originating from breast, head, and neck, prostate, non-small cell lung cancer (NSCLC), endometrial and colorectal indications using NanoString human IO panel on GeoMx DSP in combination with a complementary MultiOmyx Hyperplexed Immunofluorescence (IF) assay. The spatial and quantitative data outputs from DSP nCounter system and cell classification information from the MultiOmyx assay provided the researchers an ability not only to characterize the immunophenotypes but also to visualize the spatial distribution of tumor-infiltrating immune cells at a single-cell resolution within the TME.
Spotlight Theaters at AACR (Free AACR Whitepaper)
NanoString will be hosting two spotlight theaters during AACR (Free AACR Whitepaper) 2021. The first spotlight theater presentation is April 11 from 1:00-2:00 pm EDT, featuring Joseph Beechem, Ph.D., senior vice president of R&D and chief scientific officer for NanoString, with an overview of the latest developments in spatial biology, True spatial genomics: Measuring the transcriptome in regions, cell and sub-cellular compartments. Dr. Beechem will explain spatial technologies’ evolution and their applications from multi-cell to single-cell and subcellular resolution, using the GeoMx DSP and the company’s Spatial Molecular Imager.
The second NanoString spotlight theater is Tuesday, April 13, from 11:00-12:00 pm EDT, and is entitled: New Approaches for Cellular Therapies: Technology Symposium Featuring the GeoMx DSP and nCounter CAR-T Characterization. This panel will include three speakers, Dr. Ryan Golden, Resident Physician in Clinical Pathology, Carl June Lab, University of Pennsylvania; Dr. Marco Ruella, Assistant Professor of Medicine, University of Pennsylvania; and Ghamdan Al-Eryani, Ph.D. Student, Tumor Progression Group from the Garvan Institute. Each speaker will discuss new approaches to CAR-T characterization using the spatially-resolved and bulk RNA analysis, from understanding resistance in CART immunotherapy in lymphoma to TCR diversity in melanoma.
NanoString has launched a Technology Access Program (TAP) for the recently announced single and subcellular Spatial Molecular Imager to complement the existing TAP program for GeoMx. Under the program, customers can submit tissue samples to NanoString for analysis using the spatial profiling platforms and receive a complete data package. Researchers interested in participating in NanoString’s Technology Access Program should contact the company at [email protected].