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Series GSE200341 Query DataSets for GSE200341
Status Public on Jul 07, 2023
Title Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming [ATAC-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Decreased antigen presentation contributes to the ability of cancer cells to evade the immune system. We used the minimal gene regulatory network of type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen- presenting cells (tumor-APCs). Enforced expression of the transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient to induce cDC1 phenotype in 36 cell lines derived from human and mouse hematological and solid tumors. Within 9 days of reprogramming, tumor-APCs acquired transcriptional and epigenetic programs associated with cDC1 cells. Reprogramming restored the expression of antigen presentation complexes and costimulatory molecules on the surface of tumor cells, allowing the presentation of endogenous tumor antigens on MHC-I, and facilitating targeted killing by CD8+ T cells. Functionally, tumor-APCs engulfed and processed proteins and dead cells, secreted inflammatory cytokines, and cross- presented antigens to naïve CD8+ T cells. Human primary tumor cells could also be reprogrammed to increase their capability to present antigen and to activate patient-specific tumor-infiltrating lymphocytes. In addition to acquiring improved antigen presentation, tumor-APCs had impaired tumorigenicity in vitro and in vivo. Injection of in vitro generated melanoma-derived tumor-APCs into subcutaneous melanoma tumors delayed tumor growth and increased survival in mice. Antitumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors. Our approach serves as a platform for the development of immunotherapies that endow cancer cells with the capability to process and present endogenous tumor antigens.
 
Overall design Population ATAC-seq profiling of T98G human cancer cell line after transduction with polycystronic vectors encoding PU.1, IRF8 and BATF3 at day 3, 5, 7 and 9. ATAC-seq profilling of eGFP-transduced T98G cell line and freshly isolated peripheral blood Dendritic cells type 1 (HLA-DR+CD11C+CD141+) were used as controls.
 
Contributor(s) Zimmermannova O, Kurochkin I, Pereira C
Citation(s) 37418548
Submission date Apr 06, 2022
Last update date Sep 26, 2023
Contact name Ilia Kurochkin
E-mail(s) ilia.kurochkin@med.lu.se
Organization name Lund University
Street address BMC A12, Sölvegatan 17
City Lund
State/province Skane
ZIP/Postal code 221 84
Country Sweden
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (26)
GSM6031724 ATAC-Seq T98G rep1
GSM6031725 ATAC-Seq T98G rep2
GSM6031726 ATAC-Seq T98G rep3
This SubSeries is part of SuperSeries:
GSE224942 Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming
Relations
BioProject PRJNA824120

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
GSE200341_counts.atac.T98G.txt.gz 3.5 Mb (ftp)(http) TXT
GSE200341_meta.atac.T98G.txt.gz 238 b (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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