|
| Status |
Public on Nov 10, 2021 |
| Title |
IFNg is Critical for CAR T Cell Mediated Myeloid Activation and Induction of Endogenous Immunity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Chimeric antigen receptor (CAR) T cells mediate potent antigen-specific antitumor activity, however, their indirect effects on the endogenous immune system is not well characterized. Remarkably, we demonstrate that CAR T cell treatment of mouse syngeneic glioblastoma activates intratumoral myeloid cells and induces endogenous T cell memory responses coupled with feed-forward propagation of CAR T responses. IFNγ production by CAR T cells and IFNγ-responsiveness of host immune cells is critical for tumor immune landscape remodeling to promote a more activated and less suppressive tumor microenvironment. The clinical relevance of these observations is supported by studies showing that human IL13Rα2-CAR T cells activate patient-derived endogenous T cells and monocyte/macrophages through IFNg-signaling, as well as induce the generation of tumor-specific T cell responses in a responding patient with GBM. These studies establish that CAR T therapy has the potential to shape the tumor microenvironment, creating a context permissible for eliciting endogenous antitumor immunity.
|
| |
|
| Overall design |
CD45+ cells were sorted from untreated or CAR-T cell treated KR158-Luc tumor bearing mouse brains, 3 days after adoptive transfer and sequenced on the 10x Genomics platform
|
| |
|
| Contributor(s) |
Alizadeh D, Wong RA, Chen M, Wu X |
| Citation(s) |
33837065 |
| Submission date |
Mar 02, 2021 |
| Last update date |
Nov 11, 2021 |
| Contact name |
Steven T Rosen |
| Organization name |
City of Hope
|
| Department |
Department of Hematology and Hematopoietic Cell Transplantation
|
| Street address |
1500 E. Duarte Road
|
| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (2) |
|
| Relations |
| BioProject |
PRJNA706040 |
| SRA |
SRP308936 |
