Immunology 2023 recap: Advances in single cell and spatial technologies for immunology research
Editor's Note: Barcode Enabled Antigen Mapping (BEAM) is no longer available, but you can still analyze antigen specificity using compatible tools. Learn more here.
At Immunology 2023, the 105th annual meeting of the American Association of Immunologists (AAI), held this year in Washington, DC, scientists from around the world came together to learn more about the latest immunology research. It’s no secret that single cell and spatial techniques have advanced many areas of research, but this is particularly true for immunology, a field as diverse and complex as the immune system it’s trying to understand. In this blog post, we recap the 10x Genomics workshops presented at the conference, highlighting the utility of single cell and spatial multiomics for immunology research, and demonstrating their value over legacy technologies.
Read more to learn about our new BEAM technology for antibody discovery and T-cell therapy development, as well as how our tools are being used to delve deeper into treatment-resistant cancers.
Barcode Enabled Antigen Mapping (BEAM) takes center stage
In the first of two of our exhibitor workshops, we discussed the capabilities of our new BEAM technology to discover antigen-specific B and T cells. Led by Jose P. Jacob, Senior Product Manager, 10x Genomics, and titled, Fast track antigen-specific B- and T-cell discovery with Barcode Enabled Antigen Mapping (BEAM), the workshop focused on the power of this tool.
Seamlessly integrated with our Chromium Single Cell Immune Profiling kit, BEAM empowers rapid discovery of antigen-specific B-cell (BEAM-Ab) and T-cell (BEAM-T) clonotypes with a multiplexed antigen screening workflow. Users can acquire comprehensive antigen-specific cellular profiles—including full-length paired V(D)J sequences, gene expression, and cell surface proteins at single cell resolution—to identify rare, antigen-reactive T and B cells for accelerating therapeutic discovery.
Because of the almost infinite diversity and scale of an individual’s B- and T-cell receptor sequence repertoire, it is difficult and laborious to find an antigen-specific B cell or T cell with traditional methods/technologies. Historically, techniques like hybridoma technology and phage display have been used, but they come at a cost of time and labor. Isolating T cells specific to an antigen is also difficult, due to the nature of the cell and its binding architecture within a larger molecular complex, the major histocompatibility complex. With BEAM, researchers can essentially screen binding specificities of up to 15 antigens of interest against hundreds of thousands of B or T cells in a single experiment that only takes a week—allowing the generation of tens to hundreds of antigen-specific hits from the same sample.
BEAM can be applied to many areas, including antibody discovery and the development of cancer immunotherapies or vaccines. One example of its potential is in a use case for SARs-CoV-2 antibody discovery. Bryan Briney, PhD, Associate Professor of Immunology and Microbiology at Scripps Research Institute, recently led a collaboration with 10x Genomics scientists to recover and characterize two broadly neutralizing antibodies against a varied range of coronaviruses using a single cell multiplexed antigen screening approach, now commercialized as Barcode Enabled Antigen Mapping (BEAM). By moving from their old plate-based method, which was expensive and labor intensive, to BEAM, Briney and his team were able to probe hundreds of millions of B cells with potential specificity against barcoded antigen assemblies—enabling multiplexed antigen screening in the same sample.
Resisting the resistance: Applying single cell and spatial techniques to cancer immunotherapy
In our second workshop, Spatial transcriptomics of pancreatic premalignancies reveals cellular and molecular alterations of progression to pancreatic ductal carcinoma, speaker Luciane T. Kagohara, PhD, Associate Professor of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, summarized her work with single cell and spatial transcriptomics to study immunotherapy resistance in pancreatic and liver cancers.
Along with mentors, Dr. Elizabeth Jaffee and Dr. Elana Fertig, Dr. Kagohara published preprint work posted to bioRxiv, titled, “Spatial transcriptomics of FFPE pancreatic intraepithelial neoplasias reveals cellular and molecular alterations of progression to pancreatic ductal carcinoma,” which demonstrates the power of spatial transcriptomics to characterize cancers—at a level and resolution previously inaccessible. It also highlights how new methods can be developed to draw a much more detailed picture of what happens as lesions progress to carcinoma.
Pancreatic intraepithelial neoplasia (PanIN) is a pancreatic ductal adenocarcinoma (PDAC) pre-cancer typically diagnosed from histopathology assessment of formalin-fixed paraffin-embedded (FFPE) biopsies, which can pose a problem when it comes to single cell analyses. In their study, they built off a recently developed FFPE spatial transcriptomic approach to take a look at the transcriptional changes that occur as PanIN progresses to cancer (1). By developing a modified sample preparation workflow to perform spatial transcriptomics using Visium Spatial Gene Expression for FFPE, they were able to show that PanINs are surrounded by PDAC cancer-associated fibroblast (CAF) subtypes, including rarely seen antigen-presenting CAFs—essentially enabling them to visualize a shift between inflammatory and proliferative signaling as PanINs progress to PDAC.
Using Visium was critical for the discovery of these pre-malignancies and neighboring cancer-associated cell types. However, Dr. Kagohara needed to validate their findings at higher resolution. By employing the Xenium Analyzer, our high-throughput in situ profiling platform, the team was able to both corroborate their Visium data as well as gain new insights at subcellular resolution into these precancerous PanINs as they progress to more malignant forms.
Interested in learning more about how 10x Genomics multiomic single cell and spatial technologies are redefining immunology? Get started today.
References:
- Gracia Villacampa E, et al. Genome-wide spatial expression profiling in formalin-fixed tissues. Cell Genom 1:100065 (2021).