ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
TLR9-Targeted STAT3 Silencing Abrogates Immunosuppressive Activity of Myeloid-Derived Suppressor Cells from Prostate Cancer Patients.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Human Group IIA Secreted Phospholipase AInternational journal of molecular sciences · 2026Review
- Transcription factor targeting strategies in cancer: mechanisms, challenges and cutting-edge progress.Acta pharmacologica Sinica · 2026Review
- RelB/ILF2-GM-CSF loop sustains tumor-MDSC communication in prostate cancer immunosuppression.Cell death & disease · 2026Article
- NF-κB Signaling in Prostate Cancer Progression: Inflammatory Mediators, Survival Pathways, and Regulatory Axes.Cancers · 2026Review
- IL-6 as a central driver of immune evasion in PDAC: from IDO-mediated tolerance to multi-pathway immunosuppression.Frontiers in immunology · 2026Review
- Therapeutic Advances in Metastatic Prostate Cancer: A Journey from Standard of Care to New Emerging Treatment.International journal of molecular sciences · 2025Review
- Multimodal glioma immunotherapy combining TLR9-targeted STAT3 antisense oligodeoxynucleotides with PD1 immune checkpoint blockade.Neuro-oncology · 2025Article
- Dynamic Reprogramming of Immune-Related Signaling During Progression to Enzalutamide Resistance in Prostate Cancer.Cancers · 2025Article
- Role of the TLR signaling pathway in the pathogenesis of glioblastoma multiforme with an emphasis on immunotherapy.Biochemistry and biophysics reports · 2025Review
- Therapeutic targeting of the p300/CBP bromodomain enhances the efficacy of immune checkpoint blockade therapy.Oncogene · 2025Article
- Targeting the tumor microenvironment, a new therapeutic approach for prostate cancer.Prostate cancer and prostatic diseases · 2025Review
- Article
- Review
- Review
- Compliant immune response of silk-based biomaterials broadens application in wound treatment.Frontiers in pharmacology · 2025Review
- TLR9: A Double-Dealing Toll-Like Receptor.ImmunoTargets and therapy · 2025Review
- Tumor associated neutrophils promote prostate cancer progression by mediating neutrophil trap secretion through PSMA1- NF-κB-HIF-1α signaling axis.Frontiers in immunology · 2025Article
- Pan-cancer analysis of STAT3 indicates its potential prognostic value and correlation with immune cell infiltration in prostate cancer.Discover oncology · 2024Article
- Androgen deprivation therapy exacerbates Alzheimer's-associated cognitive decline via increased brain immune cell infiltration.Science advances · 2024Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeRecent advances in immunotherapy of advanced human cancers underscored the need to address and eliminate tumor immune evasion. The myeloid-derived suppressor cells (MDSC) are important inhibitors of T-cell responses in solid tumors, such as prostate cancers. However, targeting MDSCs proved challenging due to their phenotypic heterogeneity. EXPERIMENTAL
designMyeloid cell populations were evaluated using flow cytometry on blood samples, functional assays, and immunohistochemical/immunofluorescent stainings on specimens from healthy subjects, localized and metastatic castration-resistant prostate cancer patients.
resultsHere, we identify a population of Lin(-)CD15(HI)CD33(LO) granulocytic MDSCs that accumulate in patients' circulation during prostate cancer progression from localized to metastatic disease. The prostate cancer-associated MDSCs potently inhibit autologous CD8(+) T cells' proliferation and production of IFNγ and granzyme-B. The circulating MDSCs have high levels of activated STAT3, which is a central immune checkpoint regulator. The granulocytic pSTAT3(+) cells are also detectable in patients' prostate tissues. We previously generated an original strategy to silence genes specifically in Toll-like Receptor-9 (TLR9) positive myeloid cells using CpG-siRNA conjugates. We demonstrate that human granulocytic MDSCs express TLR9 and rapidly internalize naked CpG-STAT3siRNA, thereby silencing STAT3 expression. STAT3 blocking abrogates immunosuppressive effects of patients-derived MDSCs on effector CD8(+) T cells. These effects depended on reduced expression and enzymatic activity of Arginase-1, a downstream STAT3 target gene and a potent T-cell inhibitor.
conclusionsOverall, we demonstrate the accumulation of granulocytic MDSCs with prostate cancer progression and the feasibility of using TLR9-targeted STAT3siRNA delivery strategy to alleviate MDSC-mediated immunosuppression.
Indexed as
Identifiers
What OpenQuestion holds
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.