biostudies-literatureBraun SBarncancerfonden (Swedish Childhood Cancer Foundation)VetenskapsrådetMats Paulsson foundations, Cancera foundationFru Berta Kamprads StiftelseCancerfonden (Swedish Cancer Society)Vetenskapsrådet (Swedish Research Council)Region SkåneFru Berta Kamprads Stiftelse (Mrs. Berta Kamprad Foundation)BarncancerfondenFamiljen Erling-Perssons StiftelseKnut och Alice Wallenbergs StiftelseCancerfonden10918https://www.ebi.ac.uk/biostudies/studies/S-EPMC12680652biostudies-literatureUnknown16(1)Glioblastoma (GBM) is characterized by fast progression, infiltrative growth pattern, and a high relapse rate. A defining feature of GBM is the existence of spatially and functionally distinct cellular niches, where malignant cells engage in paracrine crosstalk with cell types comprising the tumor microenvironment. Here, we identify pericytes as the most active paracrine signaling hub within the tumor parenchyma. Their depletion through genetic engineering results in accelerated tumor progression and shortened survival. Mechanistic studies reveal that pericyte deficiency remodels the endothelium and impacts the immune cell landscape, exacerbating tumor cell invasion and immune suppression. Specifically, the pericyte-deprived endothelium recruits perivascular, tumor-associated macrophages pNature communicationsPericytes orchestrate a tumor-restraining microenvironment in glioblastoma.PMC12680652L2CancerBridgePR2024-01212023-0313624 3812 PjHarbst KPietras ABraun SBolivar PSjolund JBocci MCordero EJohansson EJonsson GBTalkhoncheh MSPhung BRosberg ROudenaarden CPietras KfalsePericytes orchestrate a tumor-restraining microenvironment in glioblastoma.Glioblastoma (GBM) is characterized by fast progression, infiltrative growth pattern, and a high relapse rate. A defining feature of GBM is the existence of spatially and functionally distinct cellular niches, where malignant cells engage in paracrine crosstalk with cell types comprising the tumor microenvironment. Here, we identify pericytes as the most active paracrine signaling hub within the tumor parenchyma. Their depletion through genetic engineering results in accelerated tumor progression and shortened survival. Mechanistic studies reveal that pericyte deficiency remodels the endothelium and impacts the immune cell landscape, exacerbating tumor cell invasion and immune suppression. Specifically, the pericyte-deprived endothelium recruits perivascular, tumor-associated macrophages p2025-01-01T00:00:00Z2025 Dec2026-07-15T14:33:36.933Z2026-07-06T03:08:38.761ZS-EPMC126806524133936010.1038/s41467-025-66985-1