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Spatial Genomics Summit Provides Sneak Peek of New Spatial Molecular Imaging Platform

By NanoString

Spatial transcriptomics, which allows scientists to locate and measure the expression of almost any gene or protein systematically with spatial context, is getting a boost from new approaches that deliver spatial insights at subcellular resolution.

NanoString, which released its GeoMx Digital Spatial Profiler (DSP) in 2019, was an early player in the field of spatial genomics and recently hosted a conference to highlight the latest innovations in multicellular, single-cell, and subcellular spatial biology.

A number of talks at the company’s fourth annual Spatial Genomics Summit shared early results from NanoString’s CosMx Spatial Molecular Imager (SMI), which is slated for commercial rollout in the second half of 2022. CosMx SMI is a high-plex in situ analysis platform that provides rapid quantification and visualization of up to 1,000 RNAs and over 100 proteins on whole tissue samples at single-cell and subcellular resolutions, acting as a complement to the multicellular spatial capabilities of the GeoMx DSP.

Initial results from the CosMx SMI indicate promising application in fields such as cancer biology and infectious disease.

For example, Jacob Estes of Oregon Health & Science University discussed a study that sought to understand the transcription profile of an HIV-infected cell and its interaction with neighboring immune cells. Currently, the human immunodeficiency virus is managed by suppressive antiretroviral therapy, but complete eradication of the virus is not possible due to the persistence of viral reservoirs in the body. The follicular dendritic cells (FDC) that reside within B cell follicles of secondary lymphoid tissues harbor more than 90 percent of the virus throughout the body, so Estes and colleagues set their sights on these follicles.

They used the GeoMx DSP to identify differentially expressed genes within the B cell follicles that were associated with cell migration, proliferation complement, and B cell signaling. Further, analysis using CosMx SMI showed that interleukin-10, an anti-inflammatory cytokine, may play a central role in differentially expressed genes within infected cell neighborhoods.

Further, Estes and team investigated the efficacy of anti-CD21 therapy and showed that it attenuated the deposition of HIV on FDC. These findings hold promise to identify specific therapeutic drug outcomes, unique inflammatory and immune biomarkers or signatures associated with pathogen persistence, and new pathways for targeted interventions to eliminate these cells in HIV cure strategies.

In another study discussed at the conference, David Ting of Massachusetts General Hospital shared an investigation into the role of repetitive elements in shaping the tumor microenvironment of pancreatic ductal adenocarcinoma.

Repetitive elements comprise at least 59 percent of the entire human genome. These mobile genetic sequences can insert copies of themselves into new locations and play an important role in shaping the genome during evolution. These elements are reactivated in early cancers and can be transmitted to surrounding cells, through extracellular vesicles, stimulating an interferon response in cells upon infection.

Using CosMx SMI on tumor tissue samples, Ting and colleagues found that repeat RNAs were initially elevated in the tumor glands and then a gradient of sorts is formed by the migration of repeat RNAs into the stromal microenvironment of the tumor. Thus, spatial transcriptomics provided an integrative way of mapping cell phenotypes, with repeat RNA localization providing novel insight into the role of repetitive elements in actual human patient tumors.

In another study demonstrating the promise of spatial genomics for cancer research, Jodi Carter of the Mayo Clinic discussed recent work in triple-negative breast cancer (TNBC), a highly aggressive cancer with a poor prognosis and no targeted treatment options.

The inhibitory immune checkpoint axis in TNBC, namely the programmed cell death protein 1 (PD-1) pathway, and its ligand PD-L1 are exploited by tumor cells to escape antitumor immune activity. Thus, inhibitors of this pathway are potential targets for cancer immunotherapy. However, unlike in other solid tumors, in TNBC, PD-L1 is expressed in varying subsets of immune cells such as macrophages.

With the use of CosMx technology, Carter was able to obtain a chemokine and a cytokine profile of PD-L1 expressing macrophages in TNBC, providing valuable insights for developing combinatorial therapies.

The complete talks, as well as other presentations highlighting applications for spatial biology, are available on demand.

This sponsored content is provided by an advertiser and published in collaboration with the GW Custom Solutions Group, a division of GenomeWeb. The content was not produced by the editors or reporters of GenomeWeb, 360Dx, or Precision Oncology News, and does not represent the views of these publications or GenomeWeb's parent company, Crain Communications Inc.