ArticleImmunity2020
The Unfolded Protein Response Mediator PERK Governs Myeloid Cell-Driven Immunosuppression in Tumors through Inhibition of STING Signaling.
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Article in Immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.
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158citing papers in PubMed
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158 citing papers in PubMed, 210 citations in OpenAlex.
- Targeting myeloid cell plasticity and metabolic reprogramming to alleviate T cell dysfunction and exhaustion-associated states and enhance immune checkpoint blockade therapy.Biomarker research · 2026Review
- The Unfolded Protein Response as a Modulator of Cancer-Immune Cell Communication in the Tumour Microenvironment.Journal of cellular and molecular medicine · 2026Review
- Inhibition of PERK signaling suppresses tumor progression and blocks GP73-GRP78-dependent stromal activation in hepatocellular carcinoma.Neoplasia (New York, N.Y.) · 2026Article
- ATF4 orchestrates cancer hallmarks: Stress adaptation, metabolic reprogramming and immune suppression.iScience · 2026Review
- β-glucan elicits APOE-dependent peripheral trained immunity to suppress hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- A prognostic model for breast cancer based on mitochondria-associated endoplasmic reticulum membrane (MAM) signature genes.Discover oncology · 2026Article
- Sphingosine kinase-2 inhibition promotes immunogenic differentiation of myeloid-derived suppressor cells through an Acetyl-CoA carboxylase-phosphatidylcholine axis.Nature communications · 2026Article
- Multifunctional nanotherapeutics for targeted modulation of endoplasmic reticulum stress to potentiate cancer therapy.Asian journal of pharmaceutical sciences · 2026Review
- An Implantable Scaffold Sequentially Releasing STING Agonist and B7-H3 Antibody for Bone Metastasis Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Ex Vivo Immuno-Oncology Platform Reveals Spatial T-cell Infiltration Patterns Linked to ATR Inhibition Responses in High-Grade Serous Ovarian Cancer.Cancer immunology research · 2026Article
- Medium-Chain Fatty Acid Receptor GPR84 Modulates Cytotoxic CD8 T-cell Antitumor Immunity through Metabolic Reprogramming.Cancer immunology research · 2026Article
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- Article
- Precision targeting of STING: Challenges, innovations, and clinical outlook for cancer therapy.Innovation (Cambridge (Mass.)) · 2026Review
- STING signaling pathway: An oasis in the glioblastoma immune desert.Theranostics · 2026Review
- KIRA6 restrains the generation of myeloid-derived suppressor cells and overcomes resistance to anti-PD-1 therapy.Cell death & disease · 2025Article
- Research progress on the mechanisms of cGAS-STING signaling in immune cell infiltration associated with vascular remodeling.Journal of translational medicine · 2025Review
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
98 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 7 institutions in 1 country.
Eslam MohamedDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Rosa A SierraDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Jimena Trillo-TinocoBristol-Myers Squibb, Devens, MA 01434, USA.
Yu CaoDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Patrick InnamaratoDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Kyle K PayneDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Alvaro de Mingo PulidoDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Jessica MandulaDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Shuzhong ZhangCenter for Microbial Pathogenesis, Nationwide Children's Hospital, Columbus, OH 43205, USA.
Paul ThevenotInstitute of Translational Research, Ochsner Health System, New Orleans, LA 70121, USA.
Subir BiswasDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Sarah K AbdallaDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Tara Lee CostichDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Kay HänggiDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Carmen M AnadonDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Elsa R FloresDepartment of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Eric B HauraDepartment of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Shikhar MehrotraDepartment of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Shari Pilon-ThomasDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Brian RuffellDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
David H MunnDepartment of Pediatrics, Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
Juan R Cubillos-RuizDepartment of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY 10065, USA; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
Jose R Conejo-GarciaDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Paulo C RodriguezDepartment of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. Electronic address: Paulo.Rodriguez@Moffitt.org.
Moffitt Cancer Center · USAugusta University Health · USBristol-Myers Squibb (United States) · USCornell University · USMedical University of South Carolina · USNationwide Children's Hospital · USOchsner Health System · US
Funding
TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI Christine O'Connell · 1998 to 2026
$93.5MIMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1MVascular Leukocytes Influence the Tumor MicroenvironmentR01CA124515 · NCI · WISTAR INSTITUTE · PI Jose R Conejo-Garcia · 2007 to 2026
$7.1MReprogramming the TME for immunogenic antigen-presentationR01CA103320 · NCI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI MUNN, DAVID H. · 2003 to 2024
$6.0MInitiation and Evolution of the Ovarian Cancer MicroenvironmentR01CA157664 · NCI · WISTAR INSTITUTE · PI CONEJO-GARCIA, JOSE R · 2011 to 2020
$3.8MFunctional reprogramming of tumor-MDSC through antibody-based therapies targeting Notch ligandsR01CA233512 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI RODRIGUEZ, PAULO CESAR · 2019 to 2023
$2.0MEffects of Common Polymorphisms in Immune Sensors in Tumor ImmunosurveillanceR01CA178687 · NCI · WISTAR INSTITUTE · PI CONEJO-GARCIA, JOSE R · 2013 to 2017
$1.9MStress Pathways in Tumors Drive Global MDSC Activity and Survival through ChopR01CA184185 · NCI · LSU HEALTH SCIENCES CENTER · PI RODRIGUEZ, PAULO CESAR · 2015 to 2019
$1.8MPTEN, Tregs and MDSCs in the tumor microenvironmentR01CA211229 · NCI · AUGUSTA UNIVERSITY · PI MUNN, DAVID H. · 2017 to 2021
$1.7MNCI NIH HHS P30 CA076292NCI NIH HHS R01 CA103320NCI NIH HHS R01 CA124515NCI NIH HHS R01 CA157664NCI NIH HHS R01 CA178687NCI NIH HHS R01 CA184185NCI NIH HHS R01 CA211229NCI NIH HHS R01 CA233512NCI NIH HHS T32 CA009140
Abstract
The primary mechanisms supporting immunoregulatory polarization of myeloid cells upon infiltration into tumors remain largely unexplored. Elucidation of these signals could enable better strategies to restore protective anti-tumor immunity. Here, we investigated the role of the intrinsic activation of the PKR-like endoplasmic reticulum (ER) kinase (PERK) in the immunoinhibitory actions of tumor-associated myeloid-derived suppressor cells (tumor-MDSCs). PERK signaling increased in tumor-MDSCs, and its deletion transformed MDSCs into myeloid cells that activated CD8
Indexed as
Gene Expression Regulation, NeoplasticAnimalsCarcinoma, Lewis LungCarcinoma, Ovarian EpithelialCD8-Positive T-LymphocyteseIF-2 KinaseFemaleHumansImmunosuppression TherapyInterferon-alphaInterferon-betaMaleMelanoma, ExperimentalMembrane ProteinsMiceMice, Inbred C57BLeIF-2 KinaseInterferon-alphaInterferon-betaMembrane ProteinsNfe2l2 protein, mouseNF-E2-Related Factor 2Receptors, InterferonSting1 protein, mouseSTING ProteinER stressMDSCsNRF2PERKSTINGtumor immunitytype I IFNunfolded protein responses
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