Fully Automated, Novel Protease-Free Workflow for Co-Detection of Protein-Protein Interaction, Individual Proteins and mRNA Using RNAscope Multiomic LS Assay

Protein-protein interaction (PPI) is one of the many mechanisms where individual cells understand and modulate the surrounding environment through communication with nearby cells or extracellular matrix. In many diseases including cancer, some PPIs have been identified to adversely impact immune response. One well-known example is the interaction between programmed cell death ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1). Tumor cells utilize PD-1/PD-L1 interaction to evade immune cell activities. 

While many immunotherapies targeting PD-1/PD-L1 blockade have been approved by FDA, there is a critical need for biomarkers that are more predictive of clinical outcomes than PD-L1 immunohistochemistry. Direct detection of PD-1/PD-L1 interactions in patient tissues in the context of a multiomic readout is likely to have better correlation to the therapeutic effect of checkpoint inhibitors than PD-L1 test alone and pinpoint specific tumor-immune cell interactions from accidental proximity. 

We have developed a fully automated workflow that can visualize PPI with multiomic context of tumor-immune microenvironment (TIME) on a single FFPE tissue section. We observed PD-1/PD-L1 interaction, individual proteins, and mRNA at high spatial resolution in tumor tissues using new workflow enabled by high sensitivity and specificity of RNAscope technology.