Longevity & AgingHuman Brain Tumor Organoid Platform Reveals Immune Responses to Glioblastoma
Researchers at UCLA developed iHOTT (immune-Human Organoid Tumor Transplantation), a platform co-culturing patient-derived glioblastoma cells with matched peripheral blood immune cells inside human cortical organoids. After 7 days, single-cell RNA sequencing confirmed preservation of all major tumor and immune populations, active cytokine secretion, and meaningful cell-cell interactions. Treating iHOTT with pembrolizumab, a PD-1 checkpoint inhibitor, reproduced cell-type shifts and T cell receptor clonal expansions seen in actual patients receiving the drug. TCR sequencing identified pembrolizumab-driven expansion of stem-like CD4 T cell clones with patient-specific repertoires, highlighting the potential of personalized antigen-targeted strategies for this notoriously immunotherapy-resistant cancer.