ArticleThe Journal of clinical investigation2020
Targeting the innate immunoreceptor RIG-I overcomes melanoma-intrinsic resistance to T cell immunotherapy.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 69 citations in OpenAlex.
- BET Inhibition Synergizes with RLR Signaling to Enhance Tumor Immunogenicity and T-cell Recognition.Cancer immunology research · 2026Article
- Oncofetal RNA-binding proteins of IGF2BP family suppress IRF-3 and NF-kB dependent transcription downstream of cytosolic RNA sensors.bioRxiv : the preprint server for biology · 2026Article
- Overcoming Immune Therapy Resistance in Cancer Through Innate Immune Reprogramming.International journal of molecular sciences · 2025Review
- PD-1 blockade treatment in melanoma: Mechanism of response and tumor-intrinsic resistance.Cancer science · 2025Review
- Harnessing innate immune pathways for therapeutic advancement in cancer.Signal transduction and targeted therapy · 2024Review
- An advanced comprehensive muti-cell-type-specific model for predicting anti-PD-1 therapeutic effect in melanoma.Theranostics · 2024Article
- Strong PD-L1 affect clinical outcomes in advanced NSCLC treated with third-generation EGFR-TKIs.Future oncology (London, England) · 2024Article
- Exploring the role of innate immunity in Cholangiocarcinoma: implications for prognosis, immune infiltration, and tumor metastasis.Journal of Cancer · 2024Article
- Current Status and Molecular Mechanisms of Resistance to Immunotherapy in Oral Malignant Melanoma.International journal of molecular sciences · 2023Review
- Systemic administration of STING agonist promotes myeloid cells maturation and antitumor immunity through regulating hematopoietic stem and progenitor cell fate.Cancer immunology, immunotherapy : CII · 2023Article
- Resveratrol induces major histocompatibility complex class I antigen presentation in a STING-dependent and independent manner in melanoma.Molecular immunology · 2023Article
- TIGIT, a novel immune checkpoint therapy for melanoma.Cell death & disease · 2023Review
- Distinct mechanisms of dysfunctional antigen-presenting DCs and monocytes by single-cell sequencing in multiple myeloma.Cancer science · 2023Article
- Activation of insulin-like growth factor-1 receptor (IGF-1R) promotes growth of colorectal cancer through triggering the MEX3A-mediated degradation of RIG-I.Acta pharmaceutica Sinica. B · 2023Article
- The m6A Reader YTHDF2 Promotes Bladder Cancer Progression by Suppressing RIG-I-Mediated Immune Response.Cancer research · 2023Article
- Local immunotherapy with the RNA-based immune stimulator CV8102 induces substantial anti-tumor responses and enhances checkpoint inhibitor activity.Cancer immunology, immunotherapy : CII · 2023Article
- Intrinsic RIG-I restrains STAT5 activation to modulate antitumor activity of CD8+ T cells.The Journal of clinical investigation · 2023Article
- Exploiting RIG-I-like receptor pathway for cancer immunotherapy.Journal of hematology & oncology · 2023Review
- Genetic dysregulation of immunologic and oncogenic signaling pathways associated with tumor-intrinsic immune resistance: a molecular basis for combination targeted therapy-immunotherapy for cancer.Cellular and molecular life sciences : CMLS · 2023Review
- Arenaviruses: Old viruses present new solutions for cancer therapy.Frontiers in immunology · 2023Review
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Authors and funding
30 authors at 10 institutions in 3 countries.
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Abstract
Understanding tumor resistance to T cell immunotherapies is critical to improve patient outcomes. Our study revealed a role for transcriptional suppression of the tumor-intrinsic HLA class I (HLA-I) antigen processing and presentation machinery (APM) in therapy resistance. Low HLA-I APM mRNA levels in melanoma metastases before immune checkpoint blockade (ICB) correlated with nonresponsiveness to therapy and poor clinical outcome. Patient-derived melanoma cells with silenced HLA-I APM escaped recognition by autologous CD8+ T cells. However, targeted activation of the innate immunoreceptor RIG-I initiated de novo HLA-I APM transcription, thereby overcoming T cell resistance. Antigen presentation was restored in interferon-sensitive (IFN-sensitive) but also immunoedited IFN-resistant melanoma models through RIG-I-dependent stimulation of an IFN-independent salvage pathway involving IRF1 and IRF3. Likewise, enhanced HLA-I APM expression was detected in RIG-Ihi (DDX58hi) melanoma biopsies, correlating with improved patient survival. Induction of HLA-I APM by RIG-I synergized with antibodies blocking PD-1 and TIGIT inhibitory checkpoints in boosting the antitumor T cell activity of ICB nonresponders. Overall, the herein-identified IFN-independent effect of RIG-I on tumor antigen presentation and T cell recognition proposes innate immunoreceptor targeting as a strategy to overcome intrinsic T cell resistance of IFN-sensitive and IFN-resistant melanomas and improve clinical outcomes in immunotherapy.
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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.