ArticleCancer immunology research2023
Inhibition of STAT6 with Antisense Oligonucleotides Enhances the Systemic Antitumor Effects of Radiotherapy and Anti-PD-1 in Metastatic Non-Small Cell Lung Cancer.
Article in Cancer immunology research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- Unlocking the therapeutic potential of immuno-radiotherapy: insights from preclinical and clinical research.Oncoimmunology · 2026Review
- DNA-PK-mediated CRTC2 phosphorylation promotes NHEJ and suppresses antitumor immunity via relocation to repair complexes.Nature communications · 2026Article
- CCL25/CCR9-induced M2 macrophage polarization promotes lung cancer progression via TGF-β1-mediated activation of the JAK/STAT-PIM2 signaling pathway.Molecular and cellular biochemistry · 2026Article
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- LncRNA PVT1 drives macrophage polarization and triple-negative breast cancer progression via PPARγ-mediated transcriptional activation.Apoptosis : an international journal on programmed cell death · 2026Article
- SOX4-STAT6-MTHFD2 axis drives hepatocellular carcinoma progression and treatment resistance.Cell death & disease · 2026Article
- STAT6 inhibition of M2 macrophages suppresses tumor growth by modulating the tumor microenvironment in colon cancer model.Frontiers in immunology · 2026Article
- Advances in neoadjuvant immunotherapy for non-small cell lung cancer.Frontiers in immunology · 2026Review
- Tumor-associated macrophages beyond M1/M2 in NSCLC: spatially organized programs, therapy resistance, and translational targeting.Frontiers in oncology · 2026Review
- The Multifaceted Roles of STAT6: Implications for Precision Immunotherapeutics.ImmunoTargets and therapy · 2026Review
- Beyond local control: radiotherapy-immunotherapy combinations fromFrontiers in genetics · 2026Review
- Suppression of tumor growth by GMI, an edible fungal immunomodulatory protein, is associated with targeting GSK3β‑mediated proteasomal degradation of PD‑L1.International journal of molecular medicine · 2025Article
- Senescent SPP1Molecular cancer · 2025Article
- Advances in RNA-based cancer therapeutics: pre-clinical and clinical implications.Molecular cancer · 2025Review
- aGenome-scale activation screen reveals lncRNA HNF1A-AS1 promotes pancreatic cancer metastasis through interacting with U2SURP to increase CD44 alternative splicing.Journal of gastroenterology · 2025Article
- Qingrehuoxue formula enhances anti-PD-1 immunotherapy in NSCLC by remodeling the tumor immune microenvironment via TREM2 signaling.BMC complementary medicine and therapies · 2025Article
- IL-4-STAT6-induced high Siglec-G/10 expression aggravates the severe immune suppressive tumor microenvironment and impedes the efficacy of immunotherapy in head and neck squamous cell carcinoma.Journal for immunotherapy of cancer · 2025Article
- Advancements in Gene Therapy for Non-Small Cell Lung Cancer: Current Approaches and Future Prospects.Genes · 2025Review
- PTP Inhibition Improves the Macrophage Antitumor Immune Response and the Efficacy of Chemo- and Radiotherapy.Cancer immunology research · 2025Article
- Oligonucleotide-Based Modulation of Macrophage Polarization: Emerging Strategies in Immunotherapy.Immunity, inflammation and disease · 2025Review
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Authors and funding
21 authors at 3 institutions in 3 countries.
Funding
Abstract
Diverse factors contribute to the limited clinical response to radiotherapy (RT) and immunotherapy in metastatic non-small cell lung cancer (NSCLC), among which is the ability of these tumors to recruit a retinue of suppressive immune cells-such as M2 tumor-associated macrophages (TAM)-thereby establishing an immunosuppressive tumor microenvironment that contributes to tumor progression and radio resistance. M2 TAMs are activated by the STAT6 signaling pathway. Therefore, we targeted STAT6 using an antisense oligonucleotide (ASO) along with hypofractionated RT (hRT; 3 fractions of 12 Gy each) to primary tumors in three bilateral murine NSCLC models (Lewis lung carcinoma, 344SQ-parental, and anti-PD-1-resistant 344SQ lung adenocarcinomas). We found that STAT6 ASO plus hRT slowed growth of both primary and abscopal tumors, decreased lung metastases, and extended survival. Interrogating the mechanism of action showed reduced M2 macrophage tumor infiltration, enhanced TH1 polarization, improved T-cell and macrophage function, and decreased TGFβ levels. The addition of anti-PD-1 further enhanced systemic antitumor responses. These results provide a preclinical rationale for the pursuit of an alternative therapeutic approach for patients with immune-resistant NSCLC.
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