@article{7006,
  keywords = {glioblastoma, immune checkpoint blockade, patient-derived organoids, pembrolizumab, single-cell RNA sequencing, Tumor Microenvironment, tumor-immune models},
  author = {Shivani Baisiwala and Elisa Fazzari and Matthew X. Li and Antoni Martija and Daria J. Azizad and Lu Sun and Gilbert Herrera and Trinh Phan and Amber Monteleone and Ryan L. Kan and David A. Nathanson and Anthony C. Wang and Won Kim and Richard G. Everson and Kunal S. Patel and Linda M. Liau and Robert M. Prins and Aparna Bhaduri},
  title = {A human tumor-immune organoid model of glioblastoma},
  abstract = {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.},
  year = {2026},
  journal = {Cell Reports},
  volume = {45},
  pages = {116790},
  month = {2026-01-27},
  issn = {2211-1247},
  url = {https://www.sciencedirect.com/science/article/pii/S2211124725015621},
  doi = {10.1016/j.celrep.2025.116790},
}