ArticleJournal of cellular and molecular medicine2024
Connexin 43 Deficiency Confers Resistance to Immunotherapy in Lung Cancer via Inhibition of the Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway.
Article in Journal of cellular and molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- cGAS-STING pathway modulation: A new hope for neural regeneration.Neural regeneration research · 2026Article
- Beyond the gap: moonlighting functions of connexins in cancer.Cell communication and signaling : CCS · 2026Review
- DC-intrinsic SHP1 restrains central memory CD8⁺ T cell formation via the TCF-1/Wnt/β-Catenin axis.Medical oncology (Northwood, London, England) · 2026Article
- SHP1 expression in tumor-associated dendritic cells drives immunoevasion via impairing CD8Oncogenesis · 2026Article
- Cell-type specific activation of the cGAS-STING pathway in tumor immunotherapy: mechanisms and therapeutic implications.Journal of translational medicine · 2026Review
- Molecular innate immune programs of tumor-associated macrophages in immune checkpoint blockade resistance: a staged framework from suppressive circuitry to translational bottlenecks.Frontiers in immunology · 2026Review
- Bridging innate and adaptive tumor immunity: cGAS-STING pathway activation to potentiate immune checkpoint blockade.Journal of experimental & clinical cancer research : CR · 2025Review
- Cardiac alterations induced by Trypanosoma cruzi extracellular vesicles and immune complexes.PLoS neglected tropical diseases · 2025Article
- Phenolic Extracts with Antioxidant and Anticancer Potential from Araticum Fruits (Annona crassiflora Mart.), a Native Brazilian Plant.Plant foods for human nutrition (Dordrecht, Netherlands) · 2025Article
- Coordination of innate immune responses by connexins.Frontiers in immunology · 2025Review
- Bibliometric analysis and visualization of Connexin 43 in the field of solid tumor research(2000-2024).Frontiers in immunology · 2025Article
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10 authors.
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Abstract
Immune checkpoint inhibitors (ICIs), especially PD-1 inhibitors, are among the first-line therapeutic drugs for the treatment of advanced non-small cell lung cancer (NSCLC). However, most patients are not sensitive to PD-1 inhibitors, and prolonged exposure can lead to acquired resistance. Thus, it is urgent to elucidate the mechanism underlying the resistance of NSCLC to ICIs. Connexin 43 (Cx43) is a gap junction (GJ) protein that is important in therapeutic efficacy to ICIs. In this study, we observed that Cx43 in murine Lewis lung carcinoma (LLC) cells mediated cyclic GMP-AMP (cGAMP) transfer to macrophages. Knockdown of Cx43 reduced T-cell activation, leading to decreased sensitivity of LLC cells to anti-PD-1 therapy. The mechanism might be that knockdown of Cx43 in LLC cells promotes macrophages differentiation into pro-tumour M2 type (TAM), thus activating the STING pathway in macrophages. These findings indicate that downregulation of Cx43 in LLC cells leads to immunotherapy resistance by negatively regulating the cGAS-STING pathway in macrophages. Therefore, Cx43/GJ-mediated signal transmission between lung cancer cells and macrophages provides new insights for increasing immunotherapy sensitivity in NSCLC.
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