ArticleJournal of the National Cancer Institute2019
STAT3 Modulation of Regulatory T Cells in Response to Radiation Therapy in Head and Neck Cancer.
Article in Journal of the National Cancer Institute, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 151 citations in OpenAlex.
- Optimizing immunotherapy for head and neck squamous cell carcinoma: recent advances and future directions.Annals of medicine · 2026Review
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- Radiotherapy and immunotherapy in cancer treatment: mechanisms of clinical synergy.The Journal of clinical investigation · 2026Review
- The Double-Edged Sword: How Radiotherapy Shapes the Tumor Immune Microenvironment to Modulate Responses to Checkpoint Inhibitors.International journal of molecular sciences · 2026Review
- Radiation as an immune modulator: mechanisms and implications for combination with immunotherapy.Nature reviews. Cancer · 2026Review
- PD-1 inhibitor improves radiosensitivity by tumor vessel normalization.British journal of cancer · 2026Article
- Fluorescence tracking Treg movement identifies anti-CCR8 and radiation as a therapeutic combination.iScience · 2026Article
- AI-based pathomics model predicts regulatory T cell infiltration and radiotherapy response in IDH-wild-type glioblastoma.Frontiers in immunology · 2026Article
- FLASH radiotherapy and immunotherapy synergy: mechanisms, strategies, and clinical translation prospects.Frontiers in immunology · 2026Review
- Cross-disciplinary communication between oral and gut microbiota in head and neck cancer.Frontiers in oncology · 2026Review
- Promising Targets and Drugs for Improving Head and Neck Cancer Response to Radiotherapy.Current pharmaceutical design · 2026Review
- Beyond local control: radiotherapy-immunotherapy combinations fromFrontiers in genetics · 2026Review
- Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.MedComm · 2025Review
- Molecular profiling of primary renal diffuse large B-cell lymphoma unravels a proclivity for immune-privileged tropism.Blood advances · 2025Article
- Current Progress and Future Directions of Immunotherapy in Head and Neck Squamous Cell Carcinoma: A Narrative Review.JAMA otolaryngology-- head & neck surgery · 2025Review
- STAT3 Signaling Pathway in Health and Disease.MedComm · 2025Review
- A strategy for synergistic enhancement of immune circulation in head and neck squamous cell carcinoma by novel nucleic acid drug therapy and immunotherapy.Journal of translational medicine · 2025Review
- Distant metastasis of oral squamous cell carcinoma: immune escape mechanism and new perspectives on treatment.Discover oncology · 2025Review
- Radiotherapy-resistant prostate cancer cells escape immune checkpoint blockade through the senescence-related ataxia telangiectasia and Rad3-related protein.Cancer communications (London, England) · 2025Article
51 more citing papers are in PubMed but not listed here.
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14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRadioresistance represents a major problem in the treatment of head and neck cancer (HNC) patients. To improve response, understanding tumor microenvironmental factors that contribute to radiation resistance is important. Regulatory T cells (Tregs) are enriched in numerous cancers and can dampen the response to radiation by creating an immune-inhibitory microenvironment. The purpose of this study was to investigate mechanisms of Treg modulation by radiation in HNC.
methodsWe utilized an orthotopic mouse model of HNC. Anti-CD25 was used for Treg depletion. Image-guided radiation was delivered to a dose of 10 Gy. Flow cytometry was used to analyze abundance and function of intratumoral immune cells. Enzyme-linked immunosorbent assay was performed to assess secreted factors. For immune-modulating therapies, anti-PD-L1, anti-CTLA-4, and STAT3 antisense oligonucleotide (ASO) were used. All statistical tests were two-sided.
resultsTreatment with anti-CD25 and radiation led to tumor eradication (57.1%, n = 4 of 7 mice), enhanced T-cell cytotoxicity compared with RT alone (CD4 effector T cells [Teff]: RT group mean = 5.37 [ 0.58] vs RT + αCD25 group mean =10.71 [0.67], P = .005; CD8 Teff: RT group mean = 9.98 [0.81] vs RT + αCD25 group mean =16.88 [2.49], P = .01) and induced tumor antigen-specific memory response (100.0%, n = 4 mice). In contrast, radiation alone or when combined with anti-CTLA4 did not lead to durable tumor control (0.0%, n = 7 mice). STAT3 inhibition in combination with radiation, but not as a single agent, improved tumor growth delay, decreased Tregs, myeloid-derived suppressor cells, and M2 macrophages and enhanced effector T cells and M1 macrophages. Experiments in nude mice inhibited the benefit of STAT3 ASO and radiation.
conclusionWe propose that STAT3 inhibition is a viable and potent therapeutic target against Tregs. Our data support the design of clinical trials integrating STAT3 ASO in the standard of care for cancer patients receiving radiation.
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