02341nas a2200433   4500000000100000008004100001260001500042653001700057653003100074653003000105653001800135653003100153653002700184653002400211100002200235700001800257700001800275700001900293700002000312700001100332700002000343700001500363700002100378700001600399700002300415700002000438700001200458700002300470700001900493700001800512700002000530700001900550245005600569856007200625300001100697490000700708520117800715022001401893       2026                            d  c2026-01-2710aglioblastoma10aimmune checkpoint blockade10apatient-derived organoids10apembrolizumab10asingle-cell RNA sequencing10aTumor Microenvironment10atumor-immune models1 aShivani Baisiwala1 aElisa Fazzari1 aMatthew X. Li1 aAntoni Martija1 aDaria J. Azizad1 aLu Sun1 aGilbert Herrera1 aTrinh Phan1 aAmber Monteleone1 aRyan L. Kan1 aDavid A. Nathanson1 aAnthony C. Wang1 aWon Kim1 aRichard G. Everson1 aKunal S. Patel1 aLinda M. Liau1 aRobert M. Prins1 aAparna Bhaduri00aA human tumor-immune organoid model of glioblastoma  uhttps://www.sciencedirect.com/science/article/pii/S2211124725015621  a1167900 v453 aA major obstacle to identifying effective therapies for the aggressive brain tumor glioblastoma is the lack of human-specific, immunocompetent models that reflect the human tumor microenvironment. To address this, we developed the immune-human organoid tumor transplantation (iHOTT) model, an autologous co-culture platform that integrates patient-derived tumor cells and matched peripheral blood mononuclear cells within human cortical organoids to enable the study of patient-specific immune responses and tumor-immune interactions. This platform preserves tumor and immune populations, immune signaling, and cell-cell interactions observed in patient tumors. Treatment of iHOTT with pembrolizumab, a checkpoint inhibitor, mirrors cell-type shifts and cell-cell interactions observed in patients. T cell receptor (TCR) sequencing further reveals pembrolizumab-driven expansion of stem-like CD4 T cell clonotypes exhibiting patient-specific repertoires. These findings establish iHOTT as a physiologically relevant platform for exploring autologous tumor-immune interactions and underscore the need for antigen-targeted strategies to enhance immunotherapy in glioblastoma.  a2211-1247