Research

Deciphering immune-regulatory functions of lymphatic endothelial cells in lymph nodes

Single-cell transcriptional analysis has demonstrated that lymph node-resident lymphatic endothelial cells are heterogenous, comprising at least three subsets conserved in mice and human that populate the floor and ceiling of the subcapsular sinus as well as medullary sinuses. Recently, we found that these subsets dynamically and differentially respond to pathological conditions, for instance in conditions of chronic dermatitis and tumor growth. Using clinically relevant animal disease models we aim to comprehensively map the heterogeneity and phenotypic responses of lymph node-resident lymphatic endothelial cells in cancer, autoimmunity, and chronic inflammatory diseases, in order to identify immune-regulatory pathways that can be exploited therapeutically.

Tumor-host communication via extracellular vesicles

Tumor-draining lymph nodes undergo massive remodeling, including changes in size, immune cell composition, and extension of lymphatic sinuses. Together, these changes may facilitate subsequent lymphatic tumor dissemination and regional metastasis. We recently found that tumor cell-derived extracellular vesicles are involved in this process. These vesicles are taken up by tumor-associated lymphatic vessels and are transported with the lymph to tumor-draining lymph nodes, where they selectively interact with lymphatic endothelial cells and lymph node-resident macrophages, induce lymph node remodeling, and impair tumor immunity. We now aim to elucidate the role of specific vesicle subtypes in these processes and the underlying molecular mechanisms in order to identify therapeutic targets. Furthermore, we explore if engineered vesicles can be used as vehicles for the specific delivery of molecular cargoes to lymph node lymphatic endothelial cells and macrophages.