Organoid Models of Tumor Immunology

Researchers present a viewpoint on recent advances, and propose translational applications of tumor organoids for immuno-oncology research, immunotherapy modeling, and precision medicine.
[Trends in Immunology]
Organoid Models of Tumor Immunology: Trends in Immunology. (n.d.). Retrieved July 16, 2020, from https://www.cell.com/trends/immunology/fulltext/S1471-4906(20)30134-4 Cite
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Evidencing a Pancreatic Ductal Adenocarcinoma Subpopulation Sensitive to the Proteasome Inhibitor Carfilzomib

Researchers selected a transcriptomic signature that predicted Carfilzomib chemosensitivity using independent component analysis on the transcriptome of pancreatic ductal adenocarcinoma (PDAC) derived primary cells cultures. They validated the signature in an independent cohort of PDAC biopsy derived pancreatic organoids.
[Clinical Cancer Research]
Fraunhoffer, N. A., Meilerman, A., Bigonnet, M., Gayet, O., Roque, J., Telle, E., Santofimia-Castaño, P., Borrello, M. T., Chuluyan, E., Dusetti, N., & Iovanna, J. (2020). Evidencing a pancreatic ductal adenocarcinoma subpopulation sensitive to the proteasome inhibitor Carfilzomib. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-20-1232 Cite
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Intestinal Organoids As Tools for Enriching and Studying Specific and Rare Cell Types: Advances and Future Directions

The authors highlight how new cell type-enriched intestinal organoids can be used to answer a diversity of questions relevant to human biology and disease.
[Journal of Molecular Cell Biology]
Intestinal organoids as tools for enriching and studying specific and rare cell types: advances and future directions | Journal of Molecular Cell Biology | Oxford Academic. (n.d.). Retrieved July 16, 2020, from https://academic.oup.com/jmcb/article/doi/10.1093/jmcb/mjaa034/5871928 Cite
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Persistence of a Regeneration-Associated, Transitional Alveolar Epithelial Cell State in Pulmonary Fibrosis

Using lung organoids, multiple in vivo repair models, single-cell transcriptomics and lineage tracing, researchers found that alveolar type-2 epithelial cells undergoing differentiation into type-1 cells acquired pre-alveolar type-1 transitional cell state en route to terminal maturation.
[Nature Cell Biology]
Kobayashi, Y., Tata, A., Konkimalla, A., Katsura, H., Lee, R. F., Ou, J., … Tata, P. R. (2020). Persistence of a regeneration-associated, transitional alveolar epithelial cell state in pulmonary fibrosis. Nature Cell Biology, 1–13. https://doi.org/10.1038/s41556-020-0542-8 Cite
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An Organoid-Based Drug Screening Identified a Menin-MLL Inhibitor for Endometrial Cancer through Regulating the HIF Pathway

CRISPR/cas9-mediated mutations of major components of the menin-MLL complex, Men1, Kmt2a and Ash2l, inhibited the growth of tumor organoids, suggesting that the complex was the target of MI-136.
[Cancer Gene Therapy]
Chen, J., Zhao, L., Peng, H., Dai, S., Quan, Y., Wang, M., Wang, J., Bi, Z., Zheng, Y., Zhou, S., Liu, Y., Chen, C., & Na, F. (2020). An organoid-based drug screening identified a menin-MLL inhibitor for endometrial cancer through regulating the HIF pathway. Cancer Gene Therapy, 1–14. https://doi.org/10.1038/s41417-020-0190-y Cite
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Patient-Specific Alzheimer-Like Pathology in Trisomy 21 Cerebral Organoids Reveals BACE2 as a Gene Dose-Sensitive AD Suppressor in Human Brain

Scientists report Alzheimer’s disease-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of Down Syndrome donors.
[Molecular Psychiatry]
Alić, I., Goh, P. A., Murray, A., Portelius, E., Gkanatsiou, E., Gough, G., Mok, K. Y., Koschut, D., Brunmeir, R., Yeap, Y. J., O’Brien, N. L., Groet, J., Shao, X., Havlicek, S., Dunn, N. R., Kvartsberg, H., Brinkmalm, G., Hithersay, R., Startin, C., … Nižetić, D. (2020). Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain. Molecular Psychiatry, 1–23. https://doi.org/10.1038/s41380-020-0806-5 Cite
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Testicular Organoid Formation Is a Property of Immature Somatic Cells, which Self-Assemble and Exhibit Long-Term Hormone-Responsive Endocrine Function

In murine organoids cultured for 14 days, tubule-like structures exhibiting a highly biomimetic architecture were characterized, including some rare germ and spermatogonial stem cells.
[Biofabrication]
Edmonds, M. E., & Woodruff, T. K. (2020). Testicular organoid formation is a property of immature somatic cells, which self-assemble and exhibit long-term hormone-responsive endocrine function. Biofabrication, 12(4), 045002. https://doi.org/10.1088/1758-5090/ab9907 Cite
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An Organoid-Based Drug Screening Identified a Menin-MLL Inhibitor for Endometrial Cancer through Regulating the HIF Pathway

CRISPR/cas9-mediated mutations of major components of the menin-MLL complex, Men1, Kmt2a and Ash2l, inhibited the growth of tumor organoids, suggesting that the complex was the target of MI-136.
[Cancer Gene Therapy]
Chen, J., Zhao, L., Peng, H., Dai, S., Quan, Y., Wang, M., Wang, J., Bi, Z., Zheng, Y., Zhou, S., Liu, Y., Chen, C., & Na, F. (2020). An organoid-based drug screening identified a menin-MLL inhibitor for endometrial cancer through regulating the HIF pathway. Cancer Gene Therapy, 1–14. https://doi.org/10.1038/s41417-020-0190-y Cite
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Probiotic Properties of Escherichia coli Nissle in Human Intestinal Organoids

To assess the safety of and protection conferred by Nissle, researchers modeled infection in stem cell-derived human intestinal organoids.
[American Society for Microbiology]
Probiotic Properties of Escherichia coli Nissle in Human Intestinal Organoids | mBio. (n.d.). Retrieved July 8, 2020, from https://mbio.asm.org/content/11/4/e01470-20 Cite
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Cancer Cells Educate Natural Killer Cells to a Metastasis-Promoting Cell State

Using ex vivo and in vivo models of metastasis, scientists established that keratin-14+ breast cancer cells were vulnerable to natural killer cells.
[Journal of Cell Biology]
Chan, I. S., Knútsdóttir, H., Ramakrishnan, G., Padmanaban, V., Warrier, M., Ramirez, J. C., Dunworth, M., Zhang, H., Jaffee, E. M., Bader, J. S., & Ewald, A. J. (2020). Cancer cells educate natural killer cells to a metastasis-promoting cell state. Journal of Cell Biology, 219(9). https://doi.org/10.1083/jcb.202001134 Cite
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Human Organoids: Model Systems for Human Biology and Medicine

The authors discuss the applications, advantages and disadvantages of human organoids as models of development and disease and outlines the challenges that have to be overcome for organoids to be able to substantially reduce the need for animal experiments.
[Nature Reviews Molecular Cell Biology]
Kim, J., Koo, B.-K., & Knoblich, J. A. (2020). Human organoids: model systems for human biology and medicine. Nature Reviews Molecular Cell Biology, 1–14. https://doi.org/10.1038/s41580-020-0259-3 Cite
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