GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE277nnn/GSE277153/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE277153GEOGSEfalseKSHV-infected endothelial cells expand and up-regulate angiogenic pathways and CXCR4 in patient-derived Kaposi sarcoma modelsKaposi sarcoma (KS) is defined by hyperangiogenesis driven by Kaposi sarcoma herpesvirus (KSHV) infected endothelial cells. The exploration of novel therapies is hampered by the lack of a patient-derived preclinical animal model. Here, we characterize patient-derived KS xenografts (PDXs) in immunodeficient NOD/SCID/gamma (NSG) mice. Thirteen cutaneous KS biopsies were subcutaneously implanted into NSG or NOG mice transgenic for human IL-6. Immunohistochemistry staining for KSHV LANA revealed that infected endothelial cells were maintained for long periods in recipient NSG. LANA+ human endothelial cells increased by a mean 4.3-fold in fifteen PDX compared to respective input biopsies, regardless of numerous implantation variables and clinical history of patient volunteers. 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.2026/07/01GSE277153GSM8515154GSM8515155GSM8515152GSM851515324676277153Homo sapiens