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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 [single cell CD45+ YUMM 2.1] |
| Organism |
Mus musculus |
| 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 it’s 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 identify the composition of the immune cell infiltrate within the tumor milieu, we analyzed the major immune cell subsets and functional categories (i.e. CD4+ T cells, CD8+ T cells, NK cells, dendritic cells, B cells, and macrophages) from the dissected tumors in mice treated with isotype control, anti-B7-H3 antibody, anti-PD1, and the combination of both antibodies using CD45+ sorted RNA-sequencing experiments.
Each sample (GSM) is multiplexed and can be demultiplexed using the information in the HTO sample. Each replicate is represented by two processed data archives appended with either '_1' or '_2'. The sequencing library was run in two separate lanes to reach a higher number of cells and reads sequenced. Each lane of data was used to produce one archive of processed data per replicate.
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| Contributor(s) |
Hsu M, Martin TC, 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 |
Oct 22, 2021 |
| Last update date |
Oct 31, 2023 |
| Contact name |
Tiphaine Christiane Martin |
| E-mail(s) |
tiphaine.martin@mssm.edu
|
| Phone |
2128248403
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| Organization name |
Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute
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| Department |
Oncological Sciences
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| Lab |
Parsons
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| Street address |
1470 Madison Ave
|
| City |
New York |
| State/province |
75459 |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| GSM5646656 |
GEX_Multiplexed_sample1 (IgGControl and anti-CD47) 3 reps |
| GSM5646657 |
HTO_Multiplexed_sample1 (IgG_Control and anti-CD47) 3 reps |
| GSM5646658 |
GEX_Multiplexed_sample2 (anti-B7-H3 and anti-B7-H3 + anti-CD47) 3 reps |
| GSM5646659 |
HTO_Multiplexed_sample2 (anti-B7-H3 and anti-B7-H3 + anti-CD47) 3 reps |
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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 |
PRJNA773709 |
| SRA |
SRP342683 |
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