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| Status |
Public on Jun 27, 2024 |
| Title |
Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy [bulk RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with inferior overall survival after ICB. Mechanistically, these phenotypes are at least partially explained by ARF6-dependent recycling, which controls plasma membrane density of the Interferon-gamma receptor. Collectively, our findings reveal the importance of endomembrane trafficking in outfitting tumour cells with the ability to shape their immune microenvironment and respond to immunotherapy.
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| |
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| Overall design |
RNASeq based comparion of gene expression between 6 Arf6null and 6 matched Arf6wt tumors
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| |
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| Contributor(s) |
Grossmann AH, Wee Y, Wang J, Wilson E, Rich CP, Rogers A, Stubben C, Wolff RK |
| Citation(s) |
39098861 |
| |
| Submission date |
Jan 12, 2024 |
| Last update date |
Aug 27, 2024 |
| Contact name |
Allie Grossmann |
| E-mail(s) |
allie.grossmann@hsc.utah.edu
|
| Organization name |
University of Utah
|
| Department |
Pathology
|
| Street address |
2000 Circle of Hope
|
| City |
Salt Lake City |
| State/province |
Utah |
| ZIP/Postal code |
84112 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE253094 |
Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy. |
|
| Relations |
| BioProject |
PRJNA1064026 |
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