After two years of virtual conferences, thousands of scientists and physicians assembled in New Orleans in April for the 2022 American Association of Cancer Research (AACR) Annual Meeting.
Spatial biology has established itself as a powerful tool for cancer research, enabling researchers to study how cells organize and interact within the tumor microenvironment and ultimately uncover the mechanisms behind cancer progression and treatment response. At AACR, there were over 20 posters featuring Akoya’s technology alone, and spatial biology was a running theme in several talks.
At our own spotlight theater session, we were joined by Sizun Jiang, PhD, from Beth Israel Deaconess Medical Center, who discussed systems approaches to spatial biology, including mapping complex cellular neighborhoods. Bernard Fox, PhD, from the Earle A. Chiles Research Institute, gave an insightful talk on why spatial phenotyping outperforms standard tools and how to develop predictive spatial signatures for immunotherapy response.
We were particularly excited to showcase the PhenoCycler™-Fusion system at this year’s conference, including a new whole-slide, 103-plex dataset. Alongside our 103-plex panel, we also gave attendees a sneak peek at our new spatial signature panels, powered by a novel universal barcoded chemistry.
Human FFPE tumor tissue labeled with a 103-plex biomarker panel
Both the 103-plex panel and the universal chemistry workflow are grounded in the same barcoded antibodies. Researchers can discover novel biomarkers using the PhenoCycler-Fusion and validate them on the high-throughput PhenoImager HT. This integrated workflow is perfectly suited for cancer research and will accelerate the translation of spatial discoveries into actionable biomarker signatures.
Rapid and deep 100-plex spatial phenotyping reveals possible mechanism for partial immunotherapy response
How many markers are enough to characterize the tumor landscape? In a first-of-its-kind spatial analysis, the Akoya Applications team and collaborators at the University of Queensland imaged a whopping 103 markers across a whole slide with single-cell resolution. The data from the study was presented as a poster at AACR and discussed by Oliver Braubach, PhD, during our spotlight theater session.
Based on the “hallmarks of cancer”, the panel was deployed on the PhenoCycler-Fusion system. It includes markers for cell lineage, immune activation and checkpoints, cellular energetics, and more. Together, these markers reveal unique insights into immune, stress and metabolic signatures to provide an integrated overview of the landscape of cancer progression.
Applying the panel to human formalin-fixed, paraffin-embedded (FFPE) tissue from oropharyngeal squamous cell carcinoma, the authors discovered 14 distinct cell types. Deep spatial phenotyping allowed them to see the complex topography of the entire tumor tissue. Whole-slide analysis uncovered 4 distinct tumor regions within the tissue with varying abundances of immune, proliferating, epithelial, and vascular cells.
Ultrahigh-plex spatial phenotyping improves pathologist annotation and gives more granular detail of the immune response mechanisms.
The authors identified distinct immune cell infiltration vs metabolic marker expression patterns corresponding with putative immune processes in each tumor region. The varying expression profiles in the tumor regions can help to decode the mechanisms of partial immunotherapy response in head and neck cancer. For example, tumor region 4 has high immune infiltration but tumor region 3 is relatively cold with low penetration by immune cells.
This study—performed in under 2 days—demonstrates the true value that rapid, whole-slide, ultrahigh-plex spatial phenotyping adds to exploratory analyses for mapping tumor architecture and uncovering the mechanisms behind clinical response and therapeutic resistance. Further details on this study are available on the poster and upcoming webinar.
Enhancing spatial signature development with a novel universal chemistry
We first announced our universal barcoded antibody chemistry at Spatial Day in December 2021. With the goal of accelerating biomarker discovery and validation, we have adopted the barcode-based antibody chemistry used on the PhenoCycler platform and integrated it with the signal amplification capabilities of Opal, part of the PhenoImager workflow.
At AACR, we pulled back the curtain for the first time to share details about this novel chemistry and the associated panel development framework. The Akoya R&D team showcased the first of these panels, the Immuno-Contexture panel—designed to assess whether the tumor is “hot” or “cold”—in a poster presented at AACR.
The spatial signature panel framework is designed to investigate specific questions about the tumor microenvironment
The team stained FFPE lung cancer tissue samples with the 6-plex panel and acquired whole-slide, multispectral scans with the PhenoImager system. They benchmarked the staining method against the clinical gold standard—DAB chromogenic IHC—and observed comparable staining patterns.
The team phenotyped each cell, observing high levels of immune cell infiltration in the tumor. The whole-slide scans were unmixed to view each marker as a monoplex stain. Combined, the markers revealed the spatial relationships between the different cell types in lung cancer.
The ability to rapidly develop and process targeted panels for investigating the tumor immune landscape will be critical for accelerating the development of spatial phenotypic signatures that reliability predict response for checkpoint inhibitor therapies.
Missed us at AACR? We hope to see you at the upcoming AAI and AGBT Annual Meetings where we will reveal more novel applications, including our first spatial transcriptomics and multiomics data using PhenoCycler-Fusion.
And if you haven’t joined us yet at one of our in-person events for the PhenoCycler-Fusion World Tour, check out the list of upcoming stops to find one near you.
Check out our other posters from the AACR meeting
- Multispectral Imaging to Detect Immune Phenotypes Within the Tumor Microenvironment in a Multi-Tissue Study: A Fully Automated 7-Color mIF Immuno-Oncology Workflow – In collaboration with LanterneDx, we demonstrated the utility of Akoya’s PD-1 /PD-L1 panel kit in studying the cellular diversity of various cancers while retaining spatial context.
- PhenoCycler (CODEX) Ultra-High Plex Single Cell Imaging of the Liver Immune Landscape to Understand the Effect of Aging and High Fat Diet on Development of Hepatocellular Carcinoma – We collaborated with the Salk Institute and Sanford Burnham Prebys Medical Discovery Institute, to use the PhenoCycler platform to identify distinct immune phenotypes present in both liver tumor tissues and high-fat-diet livers to better understand how immune dysregulation can predispose an aged and fatty liver to hepatocellular carcinoma.
- Profiling Spatial Signatures in the Microenvironment of Non Small Cell Lung Carcinomas in Immunotherapy Responsive and Resistant Disease Cohorts – In collaboration with the University of Queensland, we used a 46-plex antibody panel with the PhenoCycler-Fusion system and derived targeted 6-plex panels to run on the PhenoImager HT platform aimed at T cell profiling, immune exhaustion, and immuno modulatory targets.
- The Importance of Spatial Analysis and Multispectral Imaging When Evaluating Tumor-Immune Interactions in Glioblastoma – We worked with researchers from the City of Hope to use multispectral imaging and spatial analysis of multiple biomarkers in a single tissue sample to characterize the complex immune landscape of glioblastoma.
- Whole Slide Multispectral Imaging Reveals the Immune Subtypes of Melanoma Associated with the Tumor Microenvironment – We collaborated with LanterneDx to demonstrate the utility of Akoya’s PD-1 /PD-L1 Melanoma panel kit in studying cellular diversity while retaining spatial context. The panel analyzed the tumor microenvironment and specifically assessed immune phenotypes within various melanoma tissues.
