The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth

摘要: Glioblastoma (GBM) is the most aggressive and an incurable type of brain cancer. Human cytomegalovirus (HCMV) DNA encoded proteins, including chemokine receptor US28, have been detected in GBM tumors. US28 displays constitutive activity able to bind several human chemokines, leading activation various proliferative inflammatory signaling pathways. Here we show that HCMV, through expression significantly enhanced growth 3D spheroids U251− neurospheres primary glioblastoma cells. Moreover, accelerated cells orthotopic intracranial GBM-model mice. We developed highly potent selective US28-targeting nanobodies, which extracellular domain detect tissue. The nanobodies inhibited binding reduced US28-mediated with nanomolar potencies impaired HCMV/US28-mediated tumor vitro vivo. This study emphasizes oncomodulatory role HCMV-encoded provides a potential therapeutic approach for HCMV-positive tumors using nanobody technology.