|
| Status |
Public on May 20, 2016 |
| Title |
CIS is a potent checkpoint in NK cell-mediated tumour immunity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Natural killer (NK) cells have evolved to detect and kill aberrant cells with this activity being governed by the cytokine interleukin (IL)-15 and foreign and self-ligands. We have identified CIS (Cytokine-inducible SH2-containing protein; Cish gene) as the critical negative regulator of IL-15 signalling in NK cells. Cish was rapidly induced in response to IL-15 and deletion of Cish rendered NK cells hypersensitive to IL-15, as evidenced by superior proliferation, survival, IFN-γ production and cytotoxicity towards tumours. This was associated with enhanced JAK/STAT signalling in Cish-deleted NK cells. Correspondingly, CIS interacted with the tyrosine kinase JAK1, inhibiting its enzymatic activity and targeting JAK for proteasomal degradation. Cish-/- mice were resistant to melanoma, prostate and breast cancer metastasis in vivo, and this was intrinsic to NK cell activity. This study has uncovered a potent checkpoint in NK cell-mediated tumour immunity and holds promise for novel immunotherapies directed at blocking CIS function.
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| |
|
| Overall design |
Transcriptional profiling of ex vivo and in vitro CIS-/- nature killer cells
|
| |
|
| Contributor(s) |
Delconte RB, Kolesnik TB, Dagley LF, Shi W, Nicholson SE, Huntington ND |
| Citation(s) |
27213690 |
| |
| Submission date |
Mar 20, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Wei Shi |
| E-mail(s) |
Wei.Shi2@monash.edu
|
| Organization name |
Monash University
|
| Street address |
Wellington Rd
|
| City |
Clayton |
| State/province |
Victoria |
| ZIP/Postal code |
3800 |
| Country |
Australia |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA315771 |
| SRA |
SRP072074 |
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