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Series GSE224941 Query DataSets for GSE224941
Status Public on Jul 07, 2023
Title Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming [scRNA-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 Single-cell mRNA sequencing (scRNA-seq) was performed in T98G cells or patient-derived tumor cells transduced with hPIB-eGFP or with eGFP lentiviral particles. On 3,5,7 and 9 days after reprogramming was initiated, 5,000–10,000 transduced EGFP+ cells expressing at least one of the reprogramming markers (CD45 and HLA-DR), were separated by FACS and and subjected to sequencing.
Contributor(s) Zimmermannova O, Kurochkin I, Pereira C
Citation(s) 37418548
Submission date Feb 09, 2023
Last update date Sep 26, 2023
Contact name Ilia Kurochkin
Organization name Lund University
Street address BMC A12, Sölvegatan 17
City Lund
State/province Skane
ZIP/Postal code 221 84
Country Sweden
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (59)
GSM7035968 T98G
GSM7035969 T98G day3
GSM7035970 T98G day5
This SubSeries is part of SuperSeries:
GSE224942 Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming
BioProject PRJNA934540

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

Supplementary file Size Download File type/resource
GSE224941_Bladder.carcinoma.cnt.txt.gz 24.8 Mb (ftp)(http) TXT
GSE224941_Breast.carcinoma.cnt.txt.gz 80.5 Mb (ftp)(http) TXT
GSE224941_Lung.carcinoma.cnt.txt.gz 71.4 Mb (ftp)(http) TXT
GSE224941_Melanoma.cnt.txt.gz 250.5 Mb (ftp)(http) TXT
GSE224941_Pancreatic.carcinoma.cnt.txt.gz 37.8 Mb (ftp)(http) TXT
GSE224941_T98G.cnt.txt.gz 5.7 Mb (ftp)(http) TXT
GSE224941_Tongue.carcinoma.cnt.txt.gz 23.1 Mb (ftp)(http) TXT
GSE224941_Tonsil.carcinoma.cnt.txt.gz 94.0 Mb (ftp)(http) TXT
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