ArticleCancer immunology, immunotherapy : CII2019
An optimized retinoic acid-inducible gene I agonist M8 induces immunogenic cell death markers in human cancer cells and dendritic cell activation.
Article in Cancer immunology, immunotherapy : CII, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Designing nucleic acid-based therapeutics for cancer treatment: Updates on the state of the art.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Anti-tumor analysis of the RIG-I agonist inBiochemistry and biophysics reports · 2025Article
- Enhanced antitumor immunity of VNP20009-CCL2-CXCL9 via the cGAS/STING axis in osteosarcoma lung metastasis.Journal for immunotherapy of cancer · 2025Article
- Immunoengineering of a Photocaged 5´-triphosphate Oligoribonucleotide Ligand for Spatiotemporal Control of RIG-I Activation in Cancer.Angewandte Chemie (International ed. in English) · 2025Article
- Synthetic RIG-I-Agonist RNA Induces Death of Hepatocellular Carcinoma Cells.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2025Article
- 5' terminal nucleotide determines the immunogenicity of IVT RNAs.Nucleic acids research · 2025Article
- Role of Innate Immunity in Cancer.Advances in experimental medicine and biology · 2025Review
- Exploiting innate immunity for cancer immunotherapy.Molecular cancer · 2023Review
- The RIG-I agonist M8 triggers cell death and natural killer cell activation in human papillomavirus-associated cancer and potentiates cisplatin cytotoxicity.Cancer immunology, immunotherapy : CII · 2023Article
- Enhancing Immunogenicity in Metastatic Melanoma: Adjuvant Therapies to Promote the Anti-Tumor Immune Response.Biomedicines · 2023Review
- hMENA isoforms regulate cancer intrinsic type I IFN signaling and extrinsic mechanisms of resistance to immune checkpoint blockade in NSCLC.Journal for immunotherapy of cancer · 2023Article
- High RIG-I and EFTUD2 expression predicts poor survival in endometrial cancer.Journal of cancer research and clinical oncology · 2023Article
- RIG-I immunotherapy overcomes radioresistance in p53-positive malignant melanoma.Journal of molecular cell biology · 2023Article
- Exploiting RIG-I-like receptor pathway for cancer immunotherapy.Journal of hematology & oncology · 2023Review
- Trial watch: chemotherapy-induced immunogenic cell death in oncology.Oncoimmunology · 2023Review
- Inhibition of Galectin-9 sensitizes tumors to anthracycline treatment via inducing antitumor immunity.International journal of biological sciences · 2023Article
- Friend or foe: RIG- I like receptors and diseases.Autoimmunity reviews · 2022Review
- Inhibition of Glycolysis Impairs Retinoic Acid-Inducible Gene I-Mediated Antiviral Responses in Primary Human Dendritic Cells.Frontiers in cellular and infection microbiology · 2022Article
- Virus-like particle - mediated delivery of the RIG-I agonist M8 induces a type I interferon response and protects cells against viral infection.Frontiers in cellular and infection microbiology · 2022Article
- Leveraging NKG2D Ligands in Immuno-Oncology.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
RIG-I is a cytosolic RNA sensor that recognizes short 5' triphosphate RNA, commonly generated during virus infection. Upon activation, RIG-I initiates antiviral immunity, and in some circumstances, induces cell death. Because of this dual capacity, RIG-I has emerged as a promising target for cancer immunotherapy. Previously, a sequence-optimized RIG-I agonist (termed M8) was generated and shown to stimulate a robust immune response capable of blocking viral infection and to function as an adjuvant in vaccination strategies. Here, we investigated the potential of M8 as an anti-cancer agent by analyzing its ability to induce cell death and activate the immune response. In multiple cancer cell lines, M8 treatment strongly activated caspase 3-dependent apoptosis, that relied on an intrinsic NOXA and PUMA-driven pathway that was dependent on IFN-I signaling. Additionally, cell death induced by M8 was characterized by the expression of markers of immunogenic cell death-related damage-associated molecular patterns (ICD-DAMP)-calreticulin, HMGB1 and ATP-and high levels of ICD-related cytokines CXCL10, IFNβ, CCL2 and CXCL1. Moreover, M8 increased the levels of HLA-ABC expression on the tumor cell surface, as well as up-regulation of genes involved in antigen processing and presentation. M8 induction of the RIG-I pathway in cancer cells favored dendritic cell phagocytosis and induction of co-stimulatory molecules CD80 and CD86, together with increased expression of IL12 and CXCL10. Altogether, these results highlight the potential of M8 in cancer immunotherapy, with the capacity to induce ICD-DAMP on tumor cells and activate immunostimulatory signals that synergize with current therapies.
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