ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Mesenchymal Stromal Cells Increase the Natural Killer Resistance of Circulating Tumor Cells via Intercellular Signaling of cGAS-STING-IFNβ-HLA.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 14 citations in OpenAlex.
- Review
- TP53 Loss Elevates NF-κB-IFN-β-MHC-Ia Signaling to Promote NK Cell Resistance in Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- cGAS-STING pathway modulation: A new hope for neural regeneration.Neural regeneration research · 2026Article
- cGAS-STING pathway regulated by spatiotemporal heterogeneity of tumor microenvironment and precision therapy strategies in lung cancer.Journal of experimental & clinical cancer research : CR · 2026Review
- Prognostic significance and immune correlation of STING expression and promoter methylation in renal cell carcinoma.Scientific reports · 2026Article
- Engineering Approaches to Modify Immunomodulatory Functions of Mesenchymal Stromal Cells (MSCs): Tissue Regeneration and Clinical Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Low-dose radiotherapy remodels the tumor immune microenvironment via the cGAS-STING pathway: mechanisms, challenges, and combination therapy strategies.Molecular cancer · 2026Review
- Precision targeting of STING: Challenges, innovations, and clinical outlook for cancer therapy.Innovation (Cambridge (Mass.)) · 2026Review
- Clinical applications of circulating tumor cells in metastasis and therapy.Journal of hematology & oncology · 2025Review
- Tumor-associated mesenchymal stem/stromal cells in tumor microenvironment and carcinogenesis.Experimental hematology & oncology · 2025Review
- Demystifying the cGAS-STING pathway: precision regulation in the tumor immune microenvironment.Molecular cancer · 2025Review
- FRET-Based Sensor Zebrafish Reveal Muscle Cells Do Not Undergo Apoptosis in Starvation or Natural Aging-Induced Muscle Atrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unveiling the dual role of circulating tumor cells in colorectal cancer immunotherapy: a comprehensive review of biomarker utility and immune microenvironment crosstalk.Frontiers in immunology · 2025Review
- Agonists and Inhibitors of the cGAS-STING Pathway.Molecules (Basel, Switzerland) · 2024Review
- Mesenchymal Stromal Cells Increase the Natural Killer Resistance of Circulating Tumor Cells via Intercellular Signaling of cGAS-STING-IFNβ-HLA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Circulating tumor cells (CTCs) shed from primary tumors must overcome the cytotoxicity of immune cells, particularly natural killer (NK) cells, to cause metastasis. The tumor microenvironment (TME) protects tumor cells from the cytotoxicity of immune cells, which is partially executed by cancer-associated mesenchymal stromal cells (MSCs). However, the mechanisms by which MSCs influence the NK resistance of CTCs remain poorly understood. This study demonstrates that MSCs enhance the NK resistance of cancer cells in a gap junction-dependent manner, thereby promoting the survival and metastatic seeding of CTCs in immunocompromised mice. Tumor cells crosstalk with MSCs through an intercellular cGAS-cGAMP-STING signaling loop, leading to increased production of interferon-β (IFNβ) by MSCs. IFNβ reversely enhances the type I IFN (IFN-I) signaling in tumor cells and hence the expression of human leukocyte antigen class I (HLA-I) on the cell surface, protecting the tumor cells from NK cytotoxicity. Disruption of this loop reverses NK sensitivity in tumor cells and decreases tumor metastasis. Moreover, there are positive correlations between IFN-I signaling, HLA-I expression, and NK tolerance in human tumor samples. Thus, the NK-resistant signaling loop between tumor cells and MSCs may serve as a novel therapeutic target.
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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.