ArticleNature cancer2023
EZH2 inhibition remodels the inflammatory senescence-associated secretory phenotype to potentiate pancreatic cancer immune surveillance.
Article in Nature cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 105 citations in OpenAlex.
- Senolytic Interventions Enhance the Anti-metastatic Activity of Chemotherapy in Prostate Cancer.Cancer research · 2026Article
- Therapy induced senescence promotes immunogenicity in acute myeloid Leukemia through reduced EZH2 activity.Nature communications · 2026Article
- Reprogramming resistance in advanced lung cancer: epigenetic modulation to restore therapeutic vulnerability.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Article
- Immune surveillance and immune evasion of senescent cells.Nature reviews. Immunology · 2026Review
- Overexpression of EZH2 is associated with clinicopathological parameters and poor prognosis in gliomas.Oncology letters · 2026Article
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
- Review
- Epigenetic dynamics of cellular senescence: From mechanistic insights to precision senotherapy.Chinese medical journal · 2026Review
- Natural modulators of enhancer of zeste homolog 2 (EZH2): potential epigenetic regulators of aging-associated pathways.Biogerontology · 2026Review
- EZH2 Regulates the Proliferation-Senescence Balance and Tumor-Stromal Signaling in Lung Adenocarcinoma.International journal of molecular sciences · 2026Article
- Multiplexed cytokine and antigen mRNA administration generates durable anti-tumor immunity against pancreatic cancer.Nature communications · 2026Article
- POLY-Senolytic nanoplatform for tumor-specific eradication of senescent tumor cells and mitigation of radiotherapy-induced immune resistance of cancer.Nature communications · 2026Article
- A senescent tumor cell-derived nanovesicle directly primes splenic T cells to potentiate cancer radiotherapy.Cell reports. Medicine · 2026Article
- PSMC2 serves as a potential regulatory target of EZH2 in promoting glioma progression via epithelial-mesenchymal transition.Scientific reports · 2026Article
- Targeting senescence-like tumor-associated macrophages sensitizes chemotherapy in triple-negative breast cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- p21-Positive Senescent Stromal Cells Promote Prostate Cancer Immune Suppression and Progression That Can Be Reversed by Senolytic Therapy.Cancer discovery · 2026Article
- mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting FAM83D triggers tumor cell senescence via cGAS-STING signaling activation and reprograms TAMs to combat glioma.Journal of experimental & clinical cancer research : CR · 2026Article
- Article
36 more citing papers are in PubMed but not listed here.
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21 authors at 2 institutions in 1 country.
Funding
Abstract
Immunotherapies that produce durable responses in some malignancies have failed in pancreatic ductal adenocarcinoma (PDAC) due to rampant immune suppression and poor tumor immunogenicity. We and others have demonstrated that induction of the senescence-associated secretory phenotype (SASP) can be an effective approach to activate anti-tumor natural killer (NK) cell and T cell immunity. In the present study, we found that the pancreas tumor microenvironment suppresses NK cell and T cell surveillance after therapy-induced senescence through enhancer of zeste homolog 2 (EZH2)-mediated epigenetic repression of proinflammatory SASP genes. EZH2 blockade stimulated production of SASP chemokines CCL2 and CXCL9/10, leading to enhanced NK cell and T cell infiltration and PDAC eradication in mouse models. EZH2 activity was also associated with suppression of chemokine signaling and cytotoxic lymphocytes and reduced survival in patients with PDAC. These results demonstrate that EZH2 represses the proinflammatory SASP and that EZH2 inhibition combined with senescence-inducing therapy could be a powerful means to achieve immune-mediated tumor control in PDAC.
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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.