Immune Secrets of the Lymph Node Revealed by Spatial Genomics

Single-cell atlases mapping immune cells provide hints on how immune cells mature, attenuate, and disseminate throughout the body but lack information on spatiotemporal relationships between these cells. With the advent of spatial multiomics, we can resolve thousands of mRNAs or more than 60 protein molecules simultaneously in situ, enabling direct insight into the dynamics occurring as immune cells mature and migrate through tissue.

 

In this webinar, we will discuss a study performed on lymph node tissue sections taken from five patients using complementary spatial biology platforms: the GeoMx® Digital Spatial Profiler (DSP) and the CosMx™ Spatial Molecular Imager (SMI). With GeoMx DSP, we profiled the whole transcriptome within key structures of the lymph node including the germinal center, mantle zones, medulla, and paracortex. With CosMx SMI, we analyzed lymph node samples with clear germinal center zonation, capturing data on 1000 transcripts and 63 proteins across serial sections.'

 

Integrated results from GeoMx DSP and CosMx SMI showed that 643 pathways were enriched in dark and light zones of the germinal center or at their interface, as well as 139 key ligand-receptor interactions driving such pathways. For example, we found co-stimulation of CD28 was enriched within the light zone, and CosMx confirmed that CD86 ligands within light zone B cells were significantly co-localized with the CD28 receptors of the TfH cells of the germinal center. These findings shed light on interactions that happen at key immunological interfaces, which can be used to better understand the immune infiltrate in tumors and identify mechanisms of tumor immune evasion.

 

Learning Objectives