Year: 2026
Type: conference-abstract
Abstract: Background The tumor microenvironment (TME) is a highly structured ecosystem composed of tumor cells, immune populations, stromal cells, and extracellular matrix components that interact through complex signaling networks. These cellular interactions regulate immune activation, immune suppression, and therapeutic response. In particular, ligand–receptor interactions such as immune checkpoint signaling, cytokine communication, and growth factor signaling pathways play central roles in tumor progression and resistance to therapy. Despite their importance, detecting protein interactions directly within intact tissues remains technically challenging. Although the current generation of spatial transcriptomics and proteomics technologies provide rich information about cell identity, phenotype, and spatial organization, they primarily measure molecular abundance rather than cellular interaction. Consequently, inference of signaling relationships between cells typically relies on computational predictions based on ligand and receptor co-expression rather than direct measurement of receptor–ligand engagement.Methods To overcome these limitations, we developed an instrument for high-resolution, multiplexed, direct detection of cell–cell interactions in formalin-fixed paraffin-embedded (FFPE) tissues. Our assay is built on a proprietary version of the Proximity Ligation Assay (PLA), where paired oligo-conjugated antibodies bind to their respective receptor–ligand targets and generate detection molecules when two cells are interacting. By combining antibodies for PLA with antibodies against cell-type-specific markers, the workflow enables detection and quantification of interactions within a defined cell-type context. Our initial immuno-oncology panel targets major immune checkpoints including PD1::PD-L1 and VISTA::PSGL1; antigen presentation interactions through TCRβ::MHCII and CD8::MHCI; and co-stimulatory interactions such as CD27::CD70, while simultaneously resolving all major immune cell types.Results and Conclusions Using the Moleculent instrument, we generated first-in-class, multiplexed receptor–ligand interaction datasets across breast cancer, urothelial carcinoma, melanoma, and other tumor types. These datasets enable studies directly interrogating functional cell–cell interactions in the TME in the context of predictive biomarker discovery, immune evasion, and therapeutic response. This novel functional layer complements existing spatial Methods by capturing interactions in their native tissue environment, opening a path to a deeper mechanistic understanding of how cellular crosstalk shapes disease progression and clinical outcome.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225335004