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Series GSE200146 Query DataSets for GSE200146
Status Public on Jul 07, 2023
Title Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming [human RNA-Seq]
Organism Homo sapiens
Experiment type Expression 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 mRNAseq profiling of 17 human cancer cell lines and human embryonic fibroblasts (HEFs) after transduction with polycystronic vectors encoding PU.1, IRF8 and BATF3 at day 3, 5, 7 and 9. mRNA profilling of eGFP-transduced human cell lines and freshly isolated peripheral blood Dendritic cells type 1 (HLA-DR+CD11C+CD141+), Dendritic cells type 2 (HLA-DR+CD11C+CD141-CD1C+) and plasmacytoid dendritic cells (HLA-DR+CD11C-CD123+) were used as controls.
 
Contributor(s) Zimmermannova O, Kurochkin I, Pereira C
Citation(s) 37418548
Submission date Apr 04, 2022
Last update date Dec 15, 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 (249)
GSM6012659 PDC rep1
GSM6012660 PDC rep2
GSM6012661 PDC rep3
This SubSeries is part of SuperSeries:
GSE224942 Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming
Relations
BioProject PRJNA823054

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Supplementary file Size Download File type/resource
GSE200146_counts.Cell.Lines.txt.gz 5.1 Mb (ftp)(http) TXT
GSE200146_counts.Time.Course.txt.gz 1.9 Mb (ftp)(http) TXT
GSE200146_meta.Cell.Lines.txt.gz 927 b (ftp)(http) TXT
GSE200146_meta.Time.Course.txt.gz 376 b (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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