ArticleThe Journal of clinical investigation2021
Myeloid cell-targeted STAT3 inhibition sensitizes head and neck cancers to radiotherapy and T cell-mediated immunity.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 80 citations in OpenAlex.
- Extended-Release Immunotherapy-Eluting Embolics.Cancers · 2026Article
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- Targeting STAT3 Promotes Tumor Cell Death and Enhances T-Cell Activity in HPV16-Positive Cancer.Cancers · 2026Article
- The Multi-dimensional Mechanisms and Transformation Prospects of the Intratumoral Microbiota-Arginine Metabolism Axis in Tumor Progression and Immune Regulation.International journal of medical sciences · 2026Review
- Macrophages Drive Ferroptosis Resistance after Radiotherapy.Cancer communications (London, England) · 2026Article
- The link between macrophage polarization and response to radiotherapy in cancers: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Promising Targets and Drugs for Improving Head and Neck Cancer Response to Radiotherapy.Current pharmaceutical design · 2026Review
- Neoadjuvant immunotherapy in squamous cell carcinoma of the head and neck: current evidence and future perspectives.Molecular cancer · 2025Review
- Safety and efficacy of a STAT3-targeted cyclic oligonucleotide: From murine models to a phase 1 clinical trial in pet cats with oral cancer.Cancer cell · 2025Article
- Multimodal glioma immunotherapy combining TLR9-targeted STAT3 antisense oligodeoxynucleotides with PD1 immune checkpoint blockade.Neuro-oncology · 2025Article
- CD68- and CD163-positive tumor-associated macrophages in renal clear cell carcinoma.Scientific reports · 2025Article
- Neutrophil-specific targeting of STAT3 impairs tumor progression via the expansion of cytotoxic CD8Signal transduction and targeted therapy · 2025Article
- JAK2/STAT3 Signaling in Myeloid Cells Contributes to Obesity-Induced Inflammation and Insulin Resistance.Cells · 2025Article
- Article
- The Role of Macrophages in Various Types of Tumors and the Possibility of Their Use as Targets for Antitumor Therapy.Cancers · 2025Review
- Perineural invasion as a neuro-immune niche in head and neck cancer: mechanisms of immune evasion and therapeutic implications.Frontiers in immunology · 2025Review
- A novel mast cell marker gene-related prognostic signature to predict prognosis and reveal the immune landscape in head and neck squamous cell carcinoma.Frontiers in immunology · 2025Article
- Orchestration of Tumor-Associated Macrophages in the Tumor Cell-Macrophage-CD8International journal of biological sciences · 2025Review
- Potential regulatory mechanism and clinical significance of synaptotagmin binding cytoplasmic RNA interacting protein in colorectal cancer.World journal of clinical oncology · 2024Article
- Targeting HTR2B suppresses nonfunctioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis.Neuro-oncology · 2024Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The tumor microenvironment affects the outcome of radiotherapy against head and neck squamous cell carcinoma (HNSCC). We recently found that tolerogenic myeloid cells accumulate in the circulation of HNSCC patients undergoing radiotherapy. Here, we analyzed tumor-containing lymph node biopsies collected from these patients. After 2 weeks of radiotherapy, we found an increase in tumor-associated macrophages (TAMs) with activated STAT3, while CD8+ T cells were reduced as detected using multiplex IHC. Gene expression profiling indicated upregulation of M2 macrophage-related genes (CD163, CD206), immunosuppressive mediators (ARG1, LIF, TGFB1), and Th2 cytokines (IL4, IL5) in irradiated tumors. We next validated STAT3 as a potential target in human HNSCC-associated TAMs, using UM-SCC1 xenotransplants in humanized mice. Local injections of myeloid cell-targeted STAT3 antisense oligonucleotide (CpG-STAT3ASO) activated human DCs/macrophages and promoted CD8+ T cell recruitment, thereby arresting UM-SCC1 tumor growth. Furthermore, CpG-STAT3ASO synergized with tumor irradiation against syngeneic HPV+ mEERL and HPV- MOC2 HNSCC tumors in mice, triggering tumor regression and/or extending animal survival. The antitumor immune responses were CD8+ and CD4+ T cell dependent and associated with the activation of antigen-presenting cells (DCs/M1 macrophages) and increased CD8+ to regulatory T cell ratio. Our observations suggest that targeted inhibition of STAT3 in tumor-associated myeloid cells augments the efficacy of radiotherapy against HNSCC.
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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.