ArticleThe Journal of clinical investigation2023
Decitabine priming increases anti-PD-1 antitumor efficacy by promoting CD8+ progenitor exhausted T cell expansion in tumor models.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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The trial behind it
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Who cites it
63 citing papers in PubMed, 67 citations in OpenAlex.
- Demethylation-primed tandem CD19/CD20 CAR T cells in relapsed/refractory B-cell lymphoma: a phase I/II trial.Nature communications · 2026Trial
- A Tumor-Boundary Niche Enriched for PD-1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CDO1 as a prognostic biomarker and therapeutic target in gastric cancer: Mechanistic insights into the PI3K/AKT-THBS1 axis and epigenetic reactivation by decitabine.Clinical and translational medicine · 2026Article
- Review
- DNA Hypomethylating Agents Preserve T-cell Stemness and Potentiate the Efficacy of CD3-Bispecific Antibodies.Cancer immunology research · 2026Article
- Decoding T cell exhaustion in the tumour microenvironment.Experimental & molecular medicine · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Identification of exhausted CD8Translational cancer research · 2026Article
- The impact of T cell exhaustion in hematopoietic stem cell transplantation.Stem cell research & therapy · 2026Review
- Antigen spreading mediates heterogeneous solid tumor eradication by DNA demethylating agent-programmed CAR T cells.Science advances · 2026Article
- Structure-guided design of 7-azaindole DNMT1 inhibitors active against hypomethylating agent-resistant acute myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Endoplasmic reticulum stress-induced histone lactylation mediating immune escape of gastric cancer via PDIA6 overexpression in dendritic cells.Cell death & disease · 2026Article
- CAR-T cell exhaustion in B cell lymphoma: Current status, mechanisms, and potential solutions.Molecular therapy. Oncology · 2026Review
- RRM1 inhibition sensitizes lung adenocarcinoma to decitabine treatment.Cell death & disease · 2026Article
- Immunosuppressive tumor microenvironment and immunotherapy resistance of esophageal carcinoma.Frontiers in immunology · 2026Review
- The Double-Edged Sword of Genomic DNA Methylation: Orchestrating Gastric Carcinogenesis and Shaping Precision Oncology.Oncology research · 2026Review
- T lymphocytes and natural killer cells in myelodysplastic syndromes: function, dysfunction, and therapeutic potential.Frontiers in immunology · 2026Review
- Stem-like CD4 T cells in tumors: an emerging framework for antitumor immunity.Frontiers in immunology · 2026Review
- Cytotoxic lymphocyte heterogeneity in glioblastoma: insights from single-cell and spatial multiomics toward precision immunotherapeutic reprogramming.Frontiers in immunology · 2026Review
- Immune remodeling of tumor-draining lymph nodes: mechanistic determinants of checkpoint blockade responsiveness.Frontiers in immunology · 2026Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD8+ exhausted T cells (Tex) are heterogeneous. PD-1 inhibitors reinvigorate progenitor Tex, which subsequently differentiate into irresponsive terminal Tex. The ability to maintain a capacity for durable proliferation of progenitor Tex is important, but the mechanism remains unclear. Here, we showed CD8+ progenitor Tex pretreated with decitabine, a low-dose DNA demethylating agent, had enhanced proliferation and effector function against tumors after anti-PD-1 treatment in vitro. Treatment with decitabine plus anti-PD-1 promoted the activation and expansion of tumor-infiltrated CD8+ progenitor Tex and efficiently suppressed tumor growth in multiple tumor models. Transcriptional and epigenetic profiling of tumor-infiltrated T cells demonstrated that the combination of decitabine plus anti-PD-1 markedly elevated the clonal expansion and cytolytic activity of progenitor Tex compared with anti-PD-1 monotherapy and restrained CD8+ T cell terminal differentiation. Strikingly, decitabine plus anti-PD-1 sustained the expression and activity of the AP-1 transcription factor JunD, which was reduced following PD-1 blockade therapy. Downregulation of JunD repressed T cell proliferation, and activation of JNK/AP-1 signaling in CD8+ T cells enhanced the antitumor capacity of PD-1 inhibitors. Together, epigenetic agents remodel CD8+ progenitor Tex populations and improve responsiveness to anti-PD-1 therapy.
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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.