Glioblastoma ablates pericytes antitumor immune function through aberrant up-regulation of chaperone-mediated autophagy

摘要: The contractile perivascular cells, pericytes (PC), are hijacked by glioblastoma (GB) to facilitate tumor progression. PC's protumorigenic function requires direct interaction with cells and contributes the establishment of immunotolerance growth. Cancer up-regulate their own chaperone-mediated autophagy (CMA), a process that delivers selective cytosolic proteins lysosomes for degradation, pro-oncogenic effects. However, possible impact cancer may have on CMA surrounding host has not been explored. We analyzed contribution GB-induced changes in PC biology. found is markedly up-regulated response oxidative burst follows PC-GB cell interaction. Genetic manipulations block up-regulation allows them maintain proinflammatory support induction effective antitumor T responses required GB clearance. activity essential help show inhibition promotes death release high immunogenic levels granulocyte-macrophage colony stimulating factor (GM-CSF), through deregulation expression cell-to-cell protein secretion. A mouse model grafted vivo CMA-defective shows reduced proliferation immune compared mice control PC. Our findings identify abnormal as mechanism which elicit immunosuppressive stabilize GB-PC interactions necessary survival.