@article{1561,
  keywords = {Animals, B7-H1 Antigen, Coculture Techniques, Female, Humans, Immunotherapy, Male, Mice, Mice, Inbred BALB C, Models, Immunological, Neoplasm Proteins, Neoplasms, Experimental, organoids, PD-1, PDO, Receptors, Antigen, T-Cell, T cell receptor, TCR, Tumor Microenvironment, Cancer, checkpoint inhibitor, Immunotherapy, organoid, single-cell RNA-seq, tumor-infiltrating lymphocyte},
  author = {James T. Neal and Xingnan Li and Junjie Zhu and Valeria Giangarra and Caitlin L. Grzeskowiak and Jihang Ju and Iris H. Liu and Shin-Heng Chiou and Ameen A. Salahudeen and Amber R. Smith and Brian C. Deutsch and Lillian Liao and Allison J. Zemek and Fan Zhao and Kasper Karlsson and Liora M. Schultz and Thomas J. Metzner and Lincoln D. Nadauld and Yuen-Yi Tseng and Sahar Alkhairy and Coyin Oh and Paula Keskula and Daniel Mendoza-Villanueva and Francisco M. De La Vega and Pamela L. Kunz and Joseph C. Liao and John T. Leppert and John B. Sunwoo and Chiara Sabatti and Jesse S. Boehm and William C. Hahn and Grace X. Y. Zheng and Mark M. Davis and Calvin J. Kuo},
  title = {Organoid Modeling of the Tumor Immune Microenvironment},
  abstract = {In vitro cancer cultures, including three-dimensional organoids, typically contain exclusively neoplastic epithelium but require artificial reconstitution to recapitulate the tumor microenvironment (TME). The co-culture of primary tumor epithelia with endogenous, syngeneic tumor-infiltrating lymphocytes (TILs) as a cohesive unit has been particularly elusive. Here, an air-liquid interface (ALI) method propagated patient-derived organoids (PDOs) from >100 human biopsies or mouse tumors in syngeneic immunocompetent hosts as tumor epithelia with native embedded immune cells (T, B, NK, macrophages). Robust droplet-based, single-cell simultaneous determination of gene expression and immune repertoire indicated that PDO TILs accurately preserved the original tumor T cell receptor (TCR) spectrum. Crucially, human and murine PDOs successfully modeled immune checkpoint blockade (ICB) with anti-PD-1- and/or anti-PD-L1 expanding and activating tumor antigen-specific TILs and eliciting tumor cytotoxicity. Organoid-based propagation of primary tumor epithelium en bloc with endogenous immune stroma should enable immuno-oncology investigations within the TME and facilitate personalized immunotherapy testing.},
  year = {2018},
  journal = {Cell},
  volume = {175},
  pages = {1972-1988.e16},
  month = {2018-12-13},
  issn = {1097-4172},
  doi = {10.1016/j.cell.2018.11.021},
  language = {eng},
}