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Status |
Public on Mar 27, 2024 |
Title |
Antibody-mediated Inhibition of Global HLA/LILR Interactions Breaks Innate ImmuneSystemTolerance and Unleashes Potent Anti-Tumor Immunity |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
We have conducted a study to investigate how blocking HLA/LILR affects the activation of immune cells in the tumor microenvironment. We perfused a freshly isolated primary colon cancer biopsy sample with hIgG1 LALAPG or DX17 LALAPG for 48 hours. We then isolated CD45+ leukocytes from the tumor sample using magnetic cell sorting. Subsequently, we processed the resulting tumor-infiltrating lymphocytes (TILs) for single-cell RNA-seq and Cite-seq analysis. We compared the transcriptomes of NK cells, monocytes, and memory T cells under the two different culture conditions
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Overall design |
We utilized an oxygenated ex vivo perfusion circuit (Patent No. PCT/US2021/021525) to maintain tumors that were removed from patients in near-physiological conditions. We perfused the tumor samples with autologous patient plasma and hIgG1 LALAPG and DX17-LALAPG (5ug/ml) for 48 hours. After the perfusion was complete, we isolated tumor-infiltrated lymphocytes (TILs) by dissociating the tumor explants into a single-cell suspension. We then analyzed the TILs, including NK cells, monocytes, and T cells, in tumor microenvironments using sc-RNA-seq and CITE-seq.
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Contributor(s) |
Panda AK, Natarajan K, Teke ME, Hernandez JM, Margulies DH, Fisk B, Dulek B, Shevach E, Redekar N |
Citation missing |
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Submission date |
Mar 25, 2024 |
Last update date |
Mar 27, 2024 |
Contact name |
Ethan M Shevach |
E-mail(s) |
eshevach@niaid.nih.gov
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Organization name |
NIAID/NIH
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Street address |
10 Center Drive, Building 10, Room 11N315
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City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892 |
Country |
USA |
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Platforms (1) |
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Samples (4)
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GSM8164221 |
TILs from cells treated with hIgG1 LALAPG antibody, GEX |
GSM8164222 |
TILs from cells treated with hIgG1 LALAPG antibody, ADT |
GSM8164223 |
TILs from cells treated with DX17 LALAPG antibody, GEX |
GSM8164224 |
TILs from cells treated with DX17 LALAPG antibody, ADT |
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Relations |
BioProject |
PRJNA1091621 |
Supplementary file |
Size |
Download |
File type/resource |
GSE262381_RAW.tar |
243.8 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
GSE262381_feature_ref.csv.gz |
2.0 Kb |
(ftp)(http) |
CSV |
GSE262381_integrated_object_TILs.rds.gz |
5.5 Gb |
(ftp)(http) |
RDS |
SRA Run Selector |
Raw data are available in SRA |
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