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| 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
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| 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.
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| 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.
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| 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 |
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| |
| 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
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| Lab |
Parsons
|
| Street address |
1470 Madison Ave
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| City |
New York |
| State/province |
75459 |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (12)
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| 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 |
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| Relations |
| BioProject |
PRJNA649567 |
| SRA |
SRP274160 |
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