Enhanced glioblastoma immunotherapy via SMAC mimetic dose escalation and TGFβ blockade.

ABSTRACT:

Background

Glioblastoma (GBM) is the most common primary brain tumor with an overall survival under 21 months. Despite extensive research effort, patient outcomes have improved minimally over the past several decades. The Inhibitor of Apoptosis (IAP) proteins are critical survival factors implicated in both immune regulation and gliomagenesis. Small molecule IAP antagonists called SMAC mimetic compounds (SMCs) are under investigation as cancer therapeutics across multiple malignancies, including GBM. SMCs induce GBM cell death in the presence of inflammatory cytokines, synergize with immune checkpoint inhibitors (ICI), and induce death of microglia and macrophages. Although SMCs show significant efficacy in murine models, complete eradication is not achieved. Here, we aimed to unde

SUBMITTER: Malone K 

PROVIDER: S-EPMC12901662 | biostudies-literature | 2026 Jan-Dec

REPOSITORIES: biostudies-literature