A surgical window of opportunity trial evaluating the effect of the PCSK9 inhibitor evolocumab on tumoral MHC-I expression and CD8⁺ infiltration in glioma.

ABSTRACT: Many cancers evade immunosurveillance by downregulating surface major histocompatibility class (MHC)-I. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes MHC-I degradation and is elevated in glioma. Evolocumab is a clinically approved PCSK9 inhibitor which restores MHC-I expression in pre-clinical cancer models. However, monoclonal antibodies have limited blood brain/tumor barrier penetrance (BBB/BTB). We conducted a window-of-opportunity trial, evaluating evolocumab's BBB/BTB penetrance and biological effect (PesKE; NCT04937413). Patients with newly diagnosed or recurrent glioma undergoing a clinically indicated biopsy or resection were enrolled (n = 32, M: 16, F: 16; control average age: 51.85, evolocumab: 53). Intervention participants (n = 6) received a single subcutaneous

SUBMITTER: Singh K 

PROVIDER: S-EPMC12549866 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature