Patient-Derived Organoids Recapitulate Intrinsic Immune Landscapes and Progenitor Populations of Glioblastoma.

Watanabe, F.; Hollingsworth, E. W.; Bartley, J. M.; Wisehart, L.; Desai, R.; Hartlaub, A. M.; Hester, M. E.; Schiapparelli, P.; Hinojosa, A. Q.; Imitola, J.

doi:10.1101/2021.10.06.463228

bioRxiv · 10.1101/2021.10.06.463228

Patient-Derived Organoids Recapitulate Intrinsic Immune Landscapes and Progenitor Populations of Glioblastoma.

Watanabe, F.·Hollingsworth, E. W.·Bartley, J. M.·Wisehart, L.·Desai, R.·Hartlaub, A. M.·Hester, M. E.·Schiapparelli, P.·Hinojosa, A. Q.·Imitola, J.

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Abstract

Glioblastoma stem cells (GSCs) are highly self-renewing, resistant to therapy, and are able to form lethal tumors1, 2. Tumor organoids have been developed to study tumor evolution1-4, and while GSCs can form organoids for glioblastoma multiforme, our understanding of their intrinsic immune, metabolic, genetic, and molecular programs is limited. To address this, we deeply characterized GSC-derived GBM organoids using a modified protocol (GBMOsm) from several patient-derived GSCs and found they develop into complex 3D tissues with unique self-organization, cancerous metabolic states, and burdensome genetic landscapes. We discovered that GBMOsc recapitulate the presence of two important cell populations thought to drive GBM progression, SATB2+ and HOPX+ progenitors. Despite being devoid of immune cells, transcriptomic analysis across GBMOsc revealed an immune-like molecular program, enriched in cytokine, antigen presentation and processing, T-cell receptor inhibitors, and interferon genes. We determined that SATB2+ and HOPX+ populations contribute to this immune and interferon landscape in GBM in vivo and GBMOsm. Our work deepens our understanding of the intrinsic molecular and cellular architecture of GSC-derived GBMO and defines a novel GBMOsc intrinsic immune-like program.

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Watanabe, F., Hollingsworth, E. W., Bartley, J. M., Wisehart, L., Desai, R., Hartlaub, A. M., Hester, M. E., Schiapparelli, P., Hinojosa, A. Q., Imitola, J.. 2021-10-09. Patient-Derived Organoids Recapitulate Intrinsic Immune Landscapes and Progenitor Populations of Glioblastoma.. https://doi.org/10.1101/2021.10.06.463228

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