|
| Status |
Public on Aug 17, 2020 |
| Title |
Inhibition of MAN2A1 enhances tumor response to anti-PD-L1 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Immune checkpoint blockade (ICB) has shown remarkable efficacy, but in only a minority of cancer patients, suggesting the need to develop additional treatment strategies.We integrated transcriptional profiles of treatment-naïve human tumors and functional CRISPR screens to identify glycometabolism genes with immunomodulatory effects. We identified MAN2A1, encoding an enzyme in N-glycan maturation, as a key immunomodulatory gene. Analyses of public immune checkpoint blockade trial data also suggested a synergy between MAN2A1 inhibition and anti-PD-L1 treatment. Loss of Man2a1 in cancer cells increased their sensitivity to T cell-mediated killing. Man2a1 knockout enhanced response to anti-PD-L1 treatment and facilitated higher cytotoxic T cell infiltration in tumors under anti-PD-L1 treatment. Furthermore, a pharmacological inhibitor of MAN2A1, swainsonine, synergized with anti-PD-L1 in syngeneic melanoma tumor model, whereas each treatment alone had little effect.
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| |
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| Overall design |
Wildtype or Man2a1 knockout B16F10 treated with IgG isotype control or anti-PD-L1 or swainsonine or the combination of anti-PD-L1 and swainsonine.
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| |
|
| Contributor(s) |
Shi S, Gu S |
| Citation(s) |
32723834 |
| |
| Submission date |
Jun 21, 2020 |
| Last update date |
Nov 18, 2020 |
| Contact name |
jun ge |
| E-mail(s) |
junge960214@gmail.com
|
| Phone |
18019176603
|
| Organization name |
Tongji University
|
| Department |
School of Life Sciences and Technology
|
| Street address |
1239 Siping Road
|
| City |
Shanghai |
| ZIP/Postal code |
200000 |
| Country |
China |
| |
|
| Platforms (2) |
| GPL23479 |
BGISEQ-500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (28)
|
|
| Relations |
| BioProject |
PRJNA640958 |
| SRA |
SRP268213 |
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