| Autor: |
Jessica K. Mandula, Shiun Chang, Eslam Mohamed, Rachel Jimenez, Rosa A. Sierra-Mondragon, Darwin C. Chang, Alyssa N. Obermayer, Carlos M. Moran-Segura, Satyajit Das, Julio A. Vazquez-Martinez, Karol Prieto, Ann Chen, Keiran S.M. Smalley, Brian Czerniecki, Peter Forsyth, Richard C. Koya, Brian Ruffell, Juan R. Cubillos-Ruiz, David H. Munn, Timothy I. Shaw, Jose R. Conejo-Garcia, Paulo C. Rodriguez |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cancer cell. 40(10) |
| ISSN: |
1878-3686 |
| Popis: |
Activation of unfolded protein responses (UPRs) in cancer cells undergoing endoplasmic reticulum (ER) stress promotes survival. However, how UPR in tumor cells impacts anti-tumor immune responses remains poorly described. Here, we investigate the role of the UPR mediator pancreatic ER kinase (PKR)-like ER kinase (PERK) in cancer cells in the modulation of anti-tumor immunity. Deletion of PERK in cancer cells or pharmacological inhibition of PERK in melanoma-bearing mice incites robust activation of anti-tumor T cell immunity and attenuates tumor growth. PERK elimination in ER-stressed malignant cells triggers SEC61β-induced paraptosis, thereby promoting immunogenic cell death (ICD) and systemic anti-tumor responses. ICD induction in PERK-ablated tumors stimulates type I interferon production in dendritic cells (DCs), which primes CCR2-dependent tumor trafficking of common-monocytic precursors and their intra-tumor commitment into monocytic-lineage inflammatory Ly6C |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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