KSHV-infected endothelial cells expand and up-regulate angiogenic pathways and CXCR4 in patient-derived Kaposi sarcoma models

The Ki-67 proliferation marker overlapped with LANA+ cells, consistent with virus-driven cell expansion. Spatial transcriptome analysis revealed increased expression of viral transcripts from latent and lytic gene classes in the PDX. In addition, the expanded KSHV+ regions of the PDX maintained signature gene expression of KS tumors, with a notable enrichment in pathways associated with angiogenesis, development of endothelium, lipid transport and cell growth.

Spatial analysis revealed that fibroblasts in the KS tumor microenvironment may be one source of CXCL12 signaling to CXCR4 that was upregulated in KS tumor regions. Taken together, the reproducible expansion of KSHV-infected endothelial cells across PDX from multiple donors and the recapitulation of a KS tumor gene signature, discovers new biology and supports the application of patient-derived cutaneous KS xenografts as a pre-clinical model to test novel therapies.