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Resolving tissue heterogeneity in bone, kidney and liver cancer using in situ spatial transcriptomics

About this event

The winners of the 2021 Spatial Biology EACR & NanoString Grant program, in collaboration with Illumina, will present cancer research studies, in renal cancer, giant cell tumour of bone and hepatocellular cancer nodules, leveraging spatial biology technology.

The ‘omics revolution has driven major advances in our ability to characterise cells, including enabling an assessment of the full transcriptome. Spatial transcriptomics defines an array of technologies enabling researchers to locate transcripts in specific tissues and cells, providing an unbiased map of RNA targets. With the advent of in situ spatial transcriptomics, powered by GeoMx™ Digital Spatial Profiler, we can now accurately gather information about spatial relationships among populations of cells. The results are captivating, already facilitating novel discoveries in diverse fields, most notably in cancer.

Since in situ spatial transcriptomics is relatively new, there is much to be learned from cutting edge projects using these technologies. Our grant winners will take you to the leading edge of spatial biology and leave you with new ideas, approaches and lessons learned to inform your own research.

What will you learn?

Join the webinar to:

  • Obtain new ideas, approaches and lessons learned relating to spatial transcriptomics, from three highly innovative, award-winning presentations.
  • Learn more about using spatial transcriptomics in cancer research, including novel methods for discovering spatial biomarkers using the latest digital spatial profiling chemistry.
  • Better understand how you can apply this technology in your research.

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Presentations

TALK 1: Understanding the role of B7-H3 in renal cancer immune evasion in a spatial context

SPEAKER: Caroline Nunes-Xavier, Principal Investigator, Institute for Cancer Research, OUH & Biomarkers in Cancer, Biocruces Bizkaia Health Research Institute

ABTRACT: We are investigating the role of immune checkpoint protein B7-H3 in renal cancer. Molecular analysis using Nanostring Immune Exhaustion panel and NanoString's GeoMx Digital Spatial Profiler revealed correlations between B7-H3 expression and increased immune evasion and exhaustion. Our findings suggest a pro-oncogenic and immune evasive role for B7-H3 in renal cancer, and highlight B7-H3 as an actionable novel immune checkpoint protein in combination to targeted therapy in advanced renal cancer.

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TALK 2: Spatial transcriptomics of tumour nodules and non-tumour tissue in mice fed a Western-style diet

SPEAKER: Karolina Edlund, Postdoctoral Researcher, Leibniz Research Centre for Working Environment and Human Factors (IfADo)

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western countries. It affects approximately 25% of the population and may progress to non-alcoholic steatohepatitis (NASH) and hepatocellular cancer (HCC) in a small fraction of patients. It is essential to identify these patients very early to enable curative therapy. We here performed spatial profiling of glutamine synthetase (GS)-positive tumour nodules in mice fed a Western-style diet for 48 weeks and compared the expression to that of neighbouring GS-positive as well as GS-negative non-tumour tissue. To gain an understanding about the level of intratumoral transcriptional heterogeneity, we additionally profiled tumor areas selected from several regions within one large tumour nodule, focusing on the comparison of GS-positive versus GS-negative areas within the tumour.

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TALK 3: Disentangling cellular heterogeneity and cell-to-cell interactions in giant cell tumor of bone through spatial transcriptomics

SPEAKERS: Pavlo Lutsik, Group Leader, and Maria Llamazares Prada, Senior Scientist, both from DKFZ, German Cancer Research Center

ABSTRACT: Rare cancers affecting adolescents and young adults remain understudied. One example is giant cell tumour of bone (GCTB), a locally aggressive debilitating disease that emerges from the osteogenic differentiation lineage. GCTB is driven by a unique hotspot mutation in histone variant H3.3 through an unknown molecular mechanism. GCTB is highly heterogeneous and comprises a complex mixture of cells from hematopoietic (osteoclasts/giant cells) and mesenchymal (neoplastic stromal cells) lineages, both being insufficiently understood so far. Besides, GCTBs are macroscopically and topologically heterogeneous, with interwoven patches of tumorous and normal tissue. Thus, intricate cell-to-cell contacts and interactions between stromal and giant cell compartments, including RANK ligand signalling, are central to GCTB emergence and progression, and the detailed cross-talk picture is only emerging. However, due to its relative low incidence, efficient transcriptomic and epigenomic analysis of GCTB is complicated since most tumours are available only as FFPE blocks. Recent developments in spatial transcriptomics open now the possibility of analysing efficiently the GCTB transcriptome within the advantage of providing on top its spatial context. Thus, to gain deeper understanding of the molecular mechanisms underlying the development and progression of GCTB as well as to understand the niche maintaining tumor growth and which immune populations are present in the different tumor regions we will use spatial transcriptomics. We will also aim at elucidating if tumor or stromal cells express immune-checkpoint inhibitors and whether immunotherapy could be considered to improve their life quality and survival.

Spatial profiling would help us integrate the different datasets that we are generating and introduce the spatial context, to better understand the complexity and the cellular interactions in the disease. Thus, we recently generated comprehensive epigenomic maps of GCTB, revealing global epigenetic alterations and delayed osteogenic differentiation in H3.3-mutant cells. In order to elucidate cellular heterogeneity in GCTB and its microenvironment, map the osteogenic differentiation niche and understand the mechanisms of GCTB emergence, we are generating single-cell multi-omics datasets. However, a meaningful integration of these data is unachievable without proper understanding of GCTB spatial makeup. Due to its indisputable advantages for formalin-fixed material, nanostring/GeoMx platforms in combination with NextSeq 2000 Sequencing can be a game-changer for unravelling cellular heterogeneity and cell-to-cell interactions in this complex tumour. Through our clinical partners we can get access to abundant FFPE material that would enable comprehensive spatial transcriptomic analysis in a small cohort (8 samples) laying ground for the integration of further single-cell multi-omics datasets. On a long run this will allow us to fully utilize the power of big data for the benefit of young people suffering of this nasty tumour.

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LIVE Q&A WITH ALL SPEAKERS

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This webinar has been produced with the kind support of NanoString Technologies and Illumina. You can find out more about the technologies used in the projects presented in this webinar by visiting the NanoString Technologies and Illumina websites.

Hosted by

  • Guest speaker
    JH G
    Jan Hengstler

  • Team member
    DG T
    Diana Georgi Front Line Genomics

  • Guest speaker
    AB G
    Anna Babayan

  • Guest speaker
    AW G
    Agnese Winfield nansotring

  • Guest speaker
    KE G
    Karolina Edlund

  • Guest speaker
    ML G
    Maria Llamazares Prada

  • Guest speaker
    PL G
    Pavlo Lutsik

Front Line Genomics

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