ArticleThe Journal of experimental medicine2022
PERK reprograms hematopoietic progenitor cells to direct tumor-promoting myelopoiesis in the spleen.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
What it found
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Who cites it
31 citing papers in PubMed, 32 citations in OpenAlex.
- Anisotropic Masked Mycobacterium Potentiates Amplified Antitumor Trained Immunity via Spleen Targeting and Myelopoiesis Conversion.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- The IRE1-XBP1s Axis Drives Inflammatory Osteolysis by Regulating a 5-HT Dependent Endogenous Anti-Autophagy Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Enlarged splenic volume predicts poor survival and is associated with inflammatory imbalance in patients with diffuse large B-cell lymphoma.Blood research · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Galectin-9Aging cell · 2026Article
- KIRA6 restrains the generation of myeloid-derived suppressor cells and overcomes resistance to anti-PD-1 therapy.Cell death & disease · 2025Article
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Enhanced formation of tertiary lymphoid structures shapes the anti-tumor microenvironment in hepatocellular carcinoma after FOLFOX-HAIC therapy.Cell reports. Medicine · 2025Article
- Article
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- Myeloid cells: key players in tumor microenvironments.Frontiers of medicine · 2025Review
- MDSC checkpoint blockade therapy: a new breakthrough point overcoming immunosuppression in cancer immunotherapy.Cancer gene therapy · 2025Review
- Harnessing myeloid cells in cancer.Molecular cancer · 2025Review
- Erythroid progenitor cell-mediated spleen-tumor interaction deteriorates cancer immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- PERK-Olating Through Cancer: A Brew of Cellular Decisions.Biomolecules · 2025Review
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- The cross-talk between the macro and micro-environment in precursor lesions of pancreatic cancer leads to new and promising circulating biomarkers.Journal of experimental & clinical cancer research : CR · 2024Review
- 8th Sino-German symposium on immunology: fostering mutual trust and collaborative endeavors for advancing immunological science.Cellular & molecular immunology · 2024Article
- Loss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice.Nature communications · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The spleen is an important site of hematopoietic stem/progenitor cell (HSPC) preconditioning and tumor-promoting myeloid cell generation in cancer, but the regulatory mechanism remains unclear. Here, we found that PKR-like endoplasmic reticulum kinase (PERK) mediated HSPC reprogramming into committed MDSC precursors in the spleen via PERK-ATF4-C/EBPβ signaling. Pharmacological and genetic inhibition of this pathway in murine and human HSPCs prevented their myeloid descendant cells from becoming MDSCs even with subsequent exposure to tumor microenvironment (TME) factors. In mice, the selective delivery of PERK antagonists to the spleen was not only sufficient but more effective than the tumor-targeted strategy in preventing MDSC activation in the tumor, leading to profound TME reshaping and tumor regression. Clinically, HSPCs in the spleen of cancer patients exhibit increased PERK signaling correlated with enhanced myelopoiesis. Our findings indicate that PERK-mediated HSPC preconditioning plays a crucial role in MDSC generation, suggesting novel spleen-targeting therapeutic opportunities for restraining the tumor-promoting myeloid response at its source.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.