|
| Status |
Public on Sep 21, 2023 |
| Title |
A novel breast cancer therapeutic strategy through Hsp90 inhibition and activation of the immune system |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Low response rates and immune-related adverse events limit the impact of cancer immunotherapy. In the quest for improved clinical outcomes, preclinical studies have shown that combining immune checkpoint blockade therapies with N-terminal Hsp90 inhibitors resulted in improved efficacy, even though induction of an extensive heat shock response (HSR) with these inhibitors limited their clinical efficacy as monotherapies. We discovered that Enniatin A (EnnA) binds to the interface between the middle domains of the Hsp90 dimer and destabilizes Hsp90 client oncoproteins without inducing an HSR. We found that EnnA induces cancer cell immunogenic cell death in aggressive breast cancer models and exhibits superior anti-tumor activity compared to Hsp90 N-terminal inhibitors. Further, we show that EnnA reprograms the tumor microenvironment in syngeneic mouse models to promote CD8+ T cell-dependent anti-tumor activity mediated through the CX3CR1 signaling pathway. We propose that EnnA is a promising anti-tumor agent with a novel mechanism of action involving immunogenic cancer cell toxicity and the mobilization of CD8+ T cells into the tumor site.
|
| |
|
| Overall design |
Examination of the impact of Enniatin A (EnnA) and 17-AAG treatment on the transcriptome of murine breast cancer cell line E0771.
|
| |
|
| Contributor(s) |
Chadli A, Eisa N |
| Citation(s) |
38025772 |
| |
| Submission date |
Mar 14, 2021 |
| Last update date |
Dec 08, 2023 |
| Contact name |
Ahmed Chadli |
| E-mail(s) |
achadli@augusta.edu
|
| Phone |
7067214661
|
| Organization name |
Augusta University
|
| Department |
Cancer Center
|
| Street address |
1410 Laney Walker BLVD
|
| City |
Augusta |
| State/province |
GA |
| ZIP/Postal code |
30912 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA714405 |
| SRA |
SRP310562 |
Less...
More...