| Autor: |
Monticone, Giulia, Zhi Huang, Csibi, Fred, Leit, Silvana, Ciccone, David, Champhekar, Ameya S., Austin, Jermaine E., Ucar, Deniz A., Hossain, Fokhrul, Ibba, Salome V., Boulares, A. Hamid, Carpino, Nicholas, Xu, Keli, Majumder, Samarpan, Osborne, Barbara A., Loh, Christine, Miele, Lucio |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology; 8/26/2022, Vol. 13, p1-17, 17p |
| Abstrakt: |
A critical feature of cancer is the ability to induce immunosuppression and evade immune responses. Tumor-induced immunosuppression diminishes the effectiveness of endogenous immune responses and decreases the efficacy of cancer immunotherapy. In this study, we describe a new immunosuppressive pathway in which adenosine promotes Casitas Blineage lymphoma b (Cbl-b)-mediated Notch1 degradation, causing suppression of CD8+ T-cells effector functions. Genetic knockout and pharmacological inhibition of Cbl-b prevents Notch1 degradation in response to adenosine and reactivates its signaling. Reactivation of Notch1 results in enhanced CD8+ T-cell effector functions, anti-cancer response and resistance to immunosuppression. Our work provides evidence that targeting the Cbl-b-Notch1 axis is a novel promising strategy for cancer immunotherapy. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
