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Series GSE111360 Query DataSets for GSE111360
Status Public on Dec 13, 2018
Title Organoid modeling of the tumor immune microenvironment
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The interaction of neoplastic cells with their tumor microenvironment (TME) is required for cancer progression. However, in vitro cancer models, including recent in vitro 3-dimensional (3D) organoid cultures of primary human tumors, are typically comprised exclusively of neoplastic epithelium, with stromal and/or immune interactions requiring artificial reconstitution. As relevant to cancer immunotherapy, the unified co-culture of primary tumor epithelia with their endogenous, syngeneic tumor-infiltrating lymphocytes (TILs) as a cohesive unit has remained particularly elusive. Here, we used a single 3D air-liquid interface (ALI) methodology to successfully propagate 3D Patient-Derived Tumor Organoids (PDOs) as primary tumor epithelia together with native immune and myofibroblast stromal compartments without reconstitution. Derived from >100 diverse human surgically resected tumor samples or from murine tumors in syngeneic immunocompetent mice, PDOs preserved cancer histologic subtypes and mutational spectrum with endogenous T, B, NK cells and macrophages integrally embedded amidst the tumor epithelium. PDO-based TILs accurately recapitulated the T cell receptor (TCR) spectrum of the original tumors, as determined by a robust droplet-based immune profiling solution that links gene expression and immune repertoire in single cells. Anti-PD-1 or anti-PD-L1 treatment of organoids from murine tumors from syngeneic immunocompetent hosts induced activation and cytolytic activity of tumor antigen-specific TILs, indicating successful PDO modeling of immune checkpoint blockade (ICB) and anti-tumor immunity. Crucially, the anti-PD-1 antibody nivolumab activated TILs in PDOs from human lung, renal and melanoma clinical tumor resections. The organoid-based propagation of primary tumor epithelium en bloc with its endogenous immune stroma should facilitate mechanistic investigation of TME-specific local tumor immunity, with applications for functional testing of individualized patient immunotherapy responses.
Overall design Single cell GEX and VDJ profiling from the same samples
Contributor(s) Zheng G, Zhu J
Citation(s) 30550791
Submission date Mar 02, 2018
Last update date Mar 21, 2019
Contact name Calvin Kuo
Phone 6504985171
Organization name Stanford University
Department Department of Medicine, Division of Hematology
Street address 265 Campus Dr.
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (35)
GSM3029087 ccRCC_1_ft_gex_rep1
GSM3029088 ccRCC_1_ft_gex_rep2
GSM3029089 ccRCC_1_ft_vdj_t_rep1
BioProject PRJNA436710
SRA SRP133828

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE111360_RAW.tar 744.2 Mb (http)(custom) TAR (of CSV, MTX, TSV)
GSE111360_readme_data_processing.txt 652 b (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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