TY - JOUR
KW - glioblastoma
KW - immune checkpoint blockade
KW - patient-derived organoids
KW - pembrolizumab
KW - single-cell RNA sequencing
KW - Tumor Microenvironment
KW - tumor-immune models
AU - Shivani Baisiwala
AU - Elisa Fazzari
AU - Matthew X. Li
AU - Antoni Martija
AU - Daria J. Azizad
AU - Lu Sun
AU - Gilbert Herrera
AU - Trinh Phan
AU - Amber Monteleone
AU - Ryan L. Kan
AU - David A. Nathanson
AU - Anthony C. Wang
AU - Won Kim
AU - Richard G. Everson
AU - Kunal S. Patel
AU - Linda M. Liau
AU - Robert M. Prins
AU - Aparna Bhaduri
AB - A 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.
BT - Cell Reports
DA - 2026-01-27
DO - 10.1016/j.celrep.2025.116790
IS - 1
N2 - A 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.
PY - 2026
EP - 116790
T2 - Cell Reports
TI - A human tumor-immune organoid model of glioblastoma
UR - https://www.sciencedirect.com/science/article/pii/S2211124725015621
VL - 45
Y2 - 2026-01-28
SN - 2211-1247
ER -