Inhibition of Extracellular Matrix Protein Fibulin-3 Reduces Immunosuppressive Signaling and Increases Macrophage Activation in Glioblastoma.

ABSTRACT: Glioblastoma (GBM) tumors remain a challenge for immunotherapy owing to their heterogeneous and immunologically cold properties. GBM cells change the composition of the neural extracellular matrix (ECM), affecting the mobility, survival, and function of immune cells such as tumor-associated microglia and infiltrated macrophages (TAM). The ECM protein fibulin-3/EFEMP1 is a pericellular component uniquely upregulated in GBM compared with the normal brain, which promotes tumor growth and invasion. In this study, we demonstrate that fibulin-3 indirectly modulates TAM behavior and can be targeted to restore innate immune responses. Intracranial tumors initiated by fibulin-3-deficient GBM cells showed increased presence of TAMs with decreased immunosuppression markers (arginase-1, CD206), wherea

SUBMITTER: Kundu S 

PROVIDER: S-EPMC12423750 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature