ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
HDAC Inhibitors Enhance T-Cell Chemokine Expression and Augment Response to PD-1 Immunotherapy in Lung Adenocarcinoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers, 1 of them a synthesis that pooled it.
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Who cites it
207 citing papers in PubMed, 1 synthesis or guideline pooled it, 349 citations in OpenAlex.
- Prognostic and predictive values of CXCL10 in colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Pooled it
- First-line treatment with HDACis plus tislelizumab combined with chemotherapy in advanced NSCLC: a single-arm phase II study.The oncologist · 2025Trial
- Sintilimab (anti-PD-1 antibody) plus chidamide (histone deacetylase inhibitor) in relapsed or refractory extranodal natural killer T-cell lymphoma (SCENT): a phase Ib/II study.Signal transduction and targeted therapy · 2024Trial
- Efficacy and exploratory biomarker analysis of entinostat plus exemestane in advanced or recurrent breast cancer: phase II randomized controlled trial.Japanese journal of clinical oncology · 2023Trial
- The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma.Nature communications · 2021Trial
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- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Entinostat Enhances Antigen-Specific CD8 T-Cell Response to Immunotherapies in Lung Cancer Models.Pharmaceuticals (Basel, Switzerland) · 2026Article
- GNL3 Orchestrates AR Transcriptional Programs to Drive Castration-Resistant Prostate Cancer and Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Distinct Tumor-Immune Ecologies in Patients with Lung Cancer Predict Progression and Define a Clinical Biomarker of Therapy Response.Cancer research · 2026Article
- Preoperative exercise induces anti-tumor Kupffer cells to prevent surgical stress-promoted colorectal cancer liver metastasis.Cell reports. Medicine · 2026Article
- Biomarker guided combination strategies and perioperative integration for immune cold microsatellite stable colorectal cancer.Discover oncology · 2026Review
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Role of HDAC6 in carcinomas.Discover oncology · 2026Review
- The lactylation-immunosuppression network in cancer: driving a metabolic-epigenetic axis.Frontiers in immunology · 2026Review
- Regulation of T cell exhaustion and stemness: molecular mechanisms and implications for cancer immunotherapy.Cellular & molecular immunology · 2026Review
- Preclinical Characterization of SDFZ-8, a Highly Potent HDAC1 Inhibitor, for Cancer Immunotherapy.MedComm · 2025Article
147 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeA significant limitation of checkpoint blockade immunotherapy is the relatively low response rate (e.g., ∼20% with PD-1 blockade in lung cancer). In this study, we tested whether strategies that increase T-cell infiltration to tumors can be efficacious in enhancing immunotherapy response. EXPERIMENTAL
designWe performed an unbiased screen to identify FDA-approved oncology agents with an ability to enhance T-cell chemokine expression with the goal of identifying agents capable of augmenting immunotherapy response. Identified agents were tested in multiple lung tumor models as single agents and in combination with PD-1 blockade. Additional molecular and cellular analysis of tumors was used to define underlying mechanisms.
resultsWe found that histone deacetylase (HDAC) inhibitors (HDACi) increased expression of multiple T-cell chemokines in cancer cells, macrophages, and T cells. Using the HDACi romidepsin in vivo, we observed increased chemokine expression, enhanced T-cell infiltration, and T-cell-dependent tumor regression. Importantly, romidepsin significantly enhanced the response to PD-1 blockade immunotherapy in multiple lung tumor models, including nearly complete rejection in two models. Combined romidepsin and PD-1 blockade also significantly enhanced activation of tumor-infiltrating T cells.
conclusionsThese results provide evidence for a novel role of HDACs in modulating T-cell chemokine expression in multiple cell types. In addition, our findings indicate that pharmacologic induction of T-cell chemokine expression represents a conceptually novel approach for enhancing immunotherapy response. Finally, these results suggest that combination of HDAC inhibitors with PD-1 blockade represents a promising strategy for lung cancer treatment. Clin Cancer Res; 22(16); 4119-32. ©2016 AACR.
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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.