ArticleCancer discovery2025
Priming with DNMT Inhibitors Potentiates PD-1 Immunotherapy by Triggering Viral Mimicry in Relapsed/Refractory NK/T-cell Lymphoma.
Article in Cancer discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Liposomal mitoxantrone plus tislelizumab in patients with relapsed or refractory extranodal natural killer/T-cell lymphoma: a phase 1b/2 trial.Nature communications · 2026Trial
- Epigenetic regulatory networks in the pathogenesis and treatment of osteoporosis subtypes.Molecular biomedicine · 2026Review
- An epigenetic Achilles' heel in extranodal NK/T-cell lymphoma?Haematologica · 2026Article
- Azacitidine-induced remission enables allogeneic transplantation inHaematologica · 2026Article
- Targeting the Epigenetic-Immune Axis in Acute Myeloid Leukemia: Current Advances and Future Directions.Current oncology reports · 2026Review
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- Transposable Element Activation: A Hallmark of Cancer.Cancer discovery · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- LPAR4 mediates resistance to interferon-induced stress in soft tissue sarcoma.Science advances · 2026Article
- mNature communications · 2026Article
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Immunotherapy in NK/T-Cell Lymphoma: Mechanisms, Clinical Evidence, Resistance, and Emerging Multimodal Strategies.Cancers · 2026Review
- TAF1 Suppresses MHC-I Expression and Correlates with Poor Immunotherapy Response in Small Cell Lung Cancer.Biomedicines · 2026Article
- Class II Major Histocompatibility Complex Transactivator (CIITA): A Master MHC-II Regulator Impacting Cancer and Beyond.Journal of immunotherapy and precision oncology · 2026Review
- Transposable elements in the dark genome.Nature biotechnology · 2026Article
- Endogenous retroviruses and response to immune checkpoint inhibitors: mechanisms, clinical evidence, and therapeutic implications.Frontiers in immunology · 2026Review
- Epigenetic and metabolic plasticity of tumor cells in immunotherapy resistance.Frontiers in immunology · 2026Review
- Senescence-associated and immune-related 9p21.3 locus genes in colorectal cancer: epigenetic architecture, molecular landscape and therapeutic possibilities.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
25 authors.
Funding
Abstract
Anti-PD-1 immunotherapy has demonstrated significant antitumor efficacy in relapsed or refractory NK/T-cell lymphoma (R/R NKTL), but resistance remains a substantial challenge. In this study, we evaluate DNA methyltransferase (DNMT) inhibitors combined with anti-PD-1 mAb in 21 patients with R/R NKTL for whom prior immunotherapy failed. This combination therapy achieved an objective response rate of 66.7% (14/21), with a complete response rate of 47.6% (10/21) and a 2-year overall survival rate of 50.2%. Preclinical models revealed that anti-PD-1 resistance was linked to the absence of CD8+ T-cell infiltration and suppressed IFN pathways. DNMT inhibitors reversed these effects, restoring CD8+ T-cell activities and tumor sensitivity to PD-1 blockade. Mechanistically, DNMT inhibitors triggered DNA demethylation of endogenous retroviral elements, activating viral mimicry via upregulated endogenous nucleic acids and type I IFN signaling. These findings underscore DNMT inhibitors' role in overcoming PD-1 resistance and support their combination with anti-PD-1 as a promising strategy for R/R NKTL. SIGNIFICANCE: Resistance to anti-PD-1 immunotherapy remains a substantial challenge in R/R NKTL. In this study, we reported that combining DNMT inhibitors with anti-PD-1 mAb achieves a high complete response rate of 47.6% in immunotherapy-R/R NKTL patients. Mechanistically, DNMT inhibitors potentiate anti-PD-1 efficacy by triggering viral mimicry, remodeling the immune microenvironment and augmenting antitumor immunity.
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