NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE196142 Query DataSets for GSE196142
Status Public on Oct 31, 2023
Title Leukemia-intrinsic determinants of CAR-T response revealed by in vivo genome-wide CRISPR screening [scRNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary CAR-T cells are a promising new treatment for B cell malignancies. However, the majority of patients inevitably go on to experience disease relapse through largely unknown means. To investigate leukemia-intrinsic CAR-T resistance mechanisms, we performed genome-wide CRISPR-Cas9 loss-of-function screening in an immunocompetent murine model of B cell acute lymphoblastic leukemia (B-ALL). We identified IFN𝝲/JAK/STAT signaling and components of the antigen processing and presentation pathway as key mediators of resistance to anti-CD19 CAR-T therapy in vivo, but not in vitro. Transcriptional characterization of this model demonstrated an upregulation of these pathways in CAR-T treated relapsed tumors, and examination of data from CAR-T treated B-ALL patients revealed an association between poor outcomes and increased expression of JAK/STAT/MHC-I in leukemia cells. Together, our data identify an unexpected mechanism of resistance to immunotherapy, in which tumor cell interaction with IFN𝝲-secreting CAR-T cells in vivo activates the expression of an MHC-I inhibitory T cell program.
 
Overall design Single cell RNAseq comparison of 3 biological replicates each of mouse B-ALL cells isolated from either spleen or bone marrow challenged with CAR-T cells targeting either CD19 or a EGFRvIII
 
Contributor(s) Ramos A, Koch C, Liu Y, Hellinger RD, Kyung T, Larson RC, Fröse J, Goulet D, Doench JG, Regev A, Maus MV, Birnbaum ME, Hemann MT
Citation(s) 38052854
Submission date Feb 04, 2022
Last update date Dec 14, 2023
Contact name Charles Arthur Whittaker
E-mail(s) charliew@mit.edu
Organization name Koch Institute
Street address 77 Mass Ave 76-189
City Cambridge
State/province MA
ZIP/Postal code 02152
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (12)
GSM5861214 CTR-CAR.BM.rep1
GSM5861215 CTR-CAR.BM.rep2
GSM5861216 CTR-CAR.BM.rep3
This SubSeries is part of SuperSeries:
GSE196143 Leukemia-intrinsic determinants of CAR-T response revealed by in vivo genome-wide CRISPR screening
Relations
BioProject PRJNA803465

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
GSE196142_RAW.tar 1.1 Gb (http)(custom) TAR (of TAR)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap
External link. Please review our privacy policy.