Organoid modeling of the tumor immune microenvironment
By James T. Neal, Xingnan Li, Junjie Zhu, Valeria Giangarrà, Caitlin L. Grzeskowiak, Ji-hang Ju, Iris H Liu, S. Chiou, A. Salahudeen, A. Smith and 24 more. Cell, 2018
1,318 citations recorded by the source corpus.
SUMMARY In vitro cancer cultures, including 3-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 immunooncology investigations within the TME and facilitate personalized immunotherapy testing.
Subfields: Modeling and Simulation, Oncology, Radiology, Nuclear Medicine and Imaging
View Paper: https://www.semanticscholar.org/paper/282eb2f8feb2f17084ba82fbef7d25e1aafc92aa
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In Oncology
Citations in the corpus
- A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity. (2019, background): “Future studies involving the immune microenvironment would ideally be performed early after GBO establishment or after exogenous immune cell reconstitution (Neal et al., 2018).”
- Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion (2019, neutral): “f g NK cells (18-20) B cells (14-16) CD4+ T cells (21-25) Basophils (17)”