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Organoid Modeling of the Tumor Immune Microenvironment

Organoid Modeling of the Tumor Immune Microenvironment

James T Neal, Xingnan Li, Junjie Zhu, Valeria Giangarra, Caitlin L Grzeskowiak, Jihang Ju, Iris H Liu, Shin-Heng Chiou, Ameen A Salahudeen, Amber R Smith, Brian C Deutsch, Lillian Liao, Allison J Zemek, etc.

Cell. 2018 Dec 13;175(7):1972-1988.e16.

PMID: 30550791

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413153	CD274 from mouse			Price

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