ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Targeting Treg-Expressed STAT3 Enhances NK-Mediated Surveillance of Metastasis and Improves Therapeutic Response in Pancreatic Adenocarcinoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- Targeting regulatory T cells in the prostate cancer microenvironment: From mechanisms to therapeutics (Review).Molecular medicine reports · 2026Review
- Radiation as an immune modulator: mechanisms and implications for combination with immunotherapy.Nature reviews. Cancer · 2026Review
- Effective allogeneic natural killer cell therapy for pancreatic adenocarcinoma avails conserved activating receptors and evades HLA I-driven inhibition.Journal for immunotherapy of cancer · 2026Article
- YTHDF3 suppresses interferon-stimulated gene (ISG)-dependent antitumor immunity and promotes HPV carcinogenesis in cervical cancer.Cell death & disease · 2025Article
- The role of NK cells in regulating tumorimmunity: current state, challenges and future strategies.Cancer cell international · 2025Review
- Identification and validation of a novel lymph node metastasis-related model for papillary thyroid carcinoma to predict the prognosis.Gland surgery · 2025Article
- Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.International journal of molecular sciences · 2025Review
- Divergent response to radio-immunotherapy is defined by intrinsic features of the tumor microenvironment.Journal for immunotherapy of cancer · 2025Article
- Regulatory T cells in liver metastases: emerging and divergent roles in tumour progression.eGastroenterology · 2025Review
- Article
- The Link Between the Gut Microbiome and Bone Metastasis.International journal of molecular sciences · 2024Review
- Targeting the Dendritic Cell-Secreted Immunoregulatory Cytokine CCL22 Alleviates Radioresistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Deciphering Regulatory T-Cell Dynamics in Cancer Immunotherapy: Mechanisms, Implications, and Therapeutic Innovations.ACS pharmacology & translational science · 2024Review
- Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives.Signal transduction and targeted therapy · 2024Review
- Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma.Acta pharmacologica Sinica · 2024Article
- Necroptosis enhances 'don't eat me' signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis.Nature communications · 2024Article
- Targeting the pancreatic tumor microenvironment by plant-derived products and their nanoformulations.Medical oncology (Northwood, London, England) · 2024Review
- The preclinical gap in pancreatic cancer and radiotherapy.Disease models & mechanisms · 2024Article
- Review
- Vasculitis, CA19-9, and Perineural Invasion Differentially Predict Response and Surgical Outcome in Pancreatic Ductal Adenocarcinoma.International journal of radiation oncology, biology, physics · 2023Article
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Authors and funding
23 authors at 4 institutions in 1 country.
Funding
Abstract
purposeMetastasis remains a major hurdle in treating aggressive malignancies such as pancreatic ductal adenocarcinoma (PDAC). Improving response to treatment, therefore, requires a more detailed characterization of the cellular populations involved in controlling metastatic burden. EXPERIMENTAL
designPDAC patient tissue samples were subjected to RNA sequencing analysis to identify changes in immune infiltration following radiotherapy. Genetically engineered mouse strains in combination with orthotopic tumor models of PDAC were used to characterize disease progression. Flow cytometry was used to analyze tumor infiltrating, circulating, and nodal immune populations.
resultsWe demonstrate that although radiotherapy increases the infiltration and activation of dendritic cells (DC), it also increases the infiltration of regulatory T cells (Treg) while failing to recruit natural killer (NK) and CD8 T cells in PDAC patient tissue samples. In murine orthotopic tumor models, we show that genetic and pharmacologic depletion of Tregs and NK cells enhances and attenuates response to radiotherapy, respectively. We further demonstrate that targeted inhibition of STAT3 on Tregs results in improved control of local and distant disease progression and enhanced NK-mediated immunosurveillance of metastasis. Moreover, combination treatment of STAT3 antisense oligonucleotide (ASO) and radiotherapy invigorated systemic immune activation and conferred a survival advantage in orthotopic and metastatic tumor models. Finally, we show the response to STAT3 ASO + radiotherapy treatment is dependent on NK and DC subsets.
conclusionsOur results suggest targeting Treg-mediated immunosuppression is a critical step in mediating a response to treatment, and identifying NK cells as not only a prognostic marker of improved survival, but also as an effector population that functions to combat metastasis.
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Registered trials
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