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Series GSE155394 Query DataSets for GSE155394
Status Public on Oct 30, 2023
Title Combined blockade of B7-H3 and CD47 immune checkpoints is a new therapeutic strategy for β-catenin driven melanomas [transfection]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary In melanoma, immune cell infiltration into the tumor is associated with better patient outcomes and response to immunotherapy. T cell non-inflamed tumors (‘cold tumors’) are associated with tumor cell intrinsic Wnt/β-catenin activation, and are resistant to anti-PD-1 alone or in combination with anti-CTLA-4 therapy. Reversal of the ‘cold tumor’ phenotype and identifying new effective immunotherapies are challenges in melanoma. In a well-established preclinical melanoma model driven by β-catenin, we found that immune checkpoint molecule B7-H3 confers a suppressive tumor microenvironment by modulating antiviral signals and matricellular proteins. Its inhibition primes the microenvironment, and together with blockade of the macrophage checkpoint CD47, but not with anti-PD-1, results in synergistic anti-tumor responses. This study brings B7-H3 to the forefront as inducing a suppressive microenvironment when overexpressed, and co-targeting with CD47 as a novel combination of immune checkpoint inhibitors in melanoma that calls for testing in clinical trials.
 
Overall design To gain insight into its functions and examine the downstream effectors of B7-H3, we selected two human metastatic melanomacell lines, Hs. 688(A)T and Hs. 839T, with the highest levels of B7-H3 expression. Cells were transfected with either scrambled or B7-H3 specific siRNAs in triplicates (total 12 samples), and transcriptomes were analyzed via RNA-sequencing.
 
Contributor(s) Hsu M, Martin TC, Solovyov A, Celebi JT
Citation(s) 37086018
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 CA259295 Dissecting Phenotype Switching in Early Stage Melanomas NEW YORK UNIVERSITY SCHOOL OF MEDICINE Julide T Celebi
P30 CA196521 How do Lay Health Navigators Impact Breast Cancer Screening? (MICEO Supplement); MOUNT SINAI SCHOOL OF MEDICINE Ramon E Parsons
S10 OD018522 Transforming Genomics with 5 PB Big Omics Data Engine Cray CS300-AC Supercomputer MOUNT SINAI SCHOOL OF MEDICINE Patricia Kovatch
Submission date Jul 29, 2020
Last update date Oct 30, 2023
Contact name Tiphaine Christiane Martin
E-mail(s) tiphaine.martin@mssm.edu
Phone 2128248403
Organization name Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute
Department Oncological Sciences
Lab Parsons
Street address 1470 Madison Ave
City New York
State/province 75459
ZIP/Postal code 10029
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (12)
GSM4701024 688(A)T_siControl_1
GSM4701025 688(A)T_siControl_2
GSM4701026 688(A)T_siControl_3
This SubSeries is part of SuperSeries:
GSE161180 Combined blockade of B7-H3 and CD47 immune checkpoints is a new therapeutic strategy for β-catenin driven melanomas
Relations
BioProject PRJNA649567
SRA SRP274160

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
GSE155394_counts.xlsx 3.7 Mb (ftp)(http) XLSX
GSE155394_expression.xlsx 2.2 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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