Speaker
Description
In most types of cancer, immunosuppression limits an effective anti-cancer immune response. Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint inhibitor molecule that plays a role in various signaling processes contributing to tumor immune evasion. The aim of our research is to investigate this receptor and its family in colorectal cancer, with a particular focus on the interactions between immune cells expressing these receptors and the tumor microenvironment.
Using single-cell sequencing data, we first confirmed that LILRB4 expression is highly localized within specific myeloid immune cell subsets. To ensure high-resolution identification, we employed a specialized transcriptomics language model utilizing a novel "gene sentence" approach for cell annotation. To understand how these identified populations are modulated within the tumor architecture, we analyzed the spatial overlap between LILRB4 and its putative ligands. By characterizing receptor-ligand engagement patterns and ranking interactions through specific metrics, we were able to pinpoint the most biologically relevant pairings within the colorectal microenvironment.
Building on these identified interaction patterns, we sought to disrupt this inhibitory axis. We performed de novo protein design of a nanobody molecule optimized for high-affinity binding to the LILRB4 extracellular domain. By targeting the specific binding interface implicated in our spatial analysis, this nanobody is designed to competitively inhibit ligand engagement and reverse LILRB4-mediated immunosuppression.
Identifying the expression patterns and spatial dynamics of these molecules provides a roadmap for understanding tumor-immune interactions and suggests that LILRB4-targeted nanobodies could serve as a potent tool in colorectal cancer immunotherapy.