ArticleOncogene2021
HDAC inhibition potentiates anti-tumor activity of macrophages and enhances anti-PD-L1-mediated tumor suppression.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 1 of them a synthesis that pooled it.
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Who cites it
118 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial.Nature communications · 2024Trial
- Antibody-lectin chimeras for glyco-immune checkpoint blockade.Nature biotechnology · 2026Article
- MSCs overexpressing FGF21 alleviate acetaminophen-induced acute liver injury by eliciting macrophage-mediated phagocytosis.Hepatology communications · 2026Article
- Fast-Food Component-Induced Epigenetic Modifications Modulate Immunotherapy in Metastatic Breast Cancer.ACS omega · 2026Article
- Unveiling Lactylation: A Novel Frontier in Cancer Stemness and Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Pan-cancer analysis identifies APOC1 as a TAM-derived modulator of adaptive immune resistance and predictor of therapeutic response.Discover oncology · 2026Article
- Macrophage Plasticity: Phenotypic and Functional Profiles Across Pathological Microenvironments.International journal of molecular sciences · 2026Review
- Therapy-induced remodeling of the tumor immune microenvironment: Mechanistic insights and implications for immunotherapy.Chinese medical journal · 2026Review
- In vivo CAR-cell therapy: current challenges and emerging therapeutic advances.Molecular biomedicine · 2026Review
- Histone deacetylases: Function in tumor development and therapeutic prospects (Review).Oncology letters · 2026Review
- The double-edged sword role of tumor-associated macrophages: preventing or causing resistance to immunotherapy.Journal of experimental & clinical cancer research : CR · 2026Review
- Macrophages: Targets for next-generation cancer immunotherapy.Cancer cell · 2026Review
- Epigenetic programming of macrophages across inflammatory and malignant diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Epigenetic modulation to overcome immune suppression in pancreatic cancer.Clinical epigenetics · 2026Review
- Review
- HDAC inhibitors in cancer therapy: sensitization mechanisms, combination strategies, and translational challenges.Frontiers in cell and developmental biology · 2026Review
- Reprogramming tumor-associated macrophages in DMG/DIPG: emerging molecular and biophysical strategies.Frontiers in immunology · 2026Review
- Role of Trichostatin A (TSA) in modulating the epigenetic modification in the lymphocytes of colorectal cancer (CRC).Clinical epigenetics · 2025Article
58 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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the widespread use of the blockade of immune checkpoints, for a significant number of cancer patients, these therapies have proven ineffective, presumably due to the immunosuppressive nature of the tumor microenvironment (TME). Critical drivers of immune escape in the TME include tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), which not only mediate immune suppression, but also facilitate metastatic dissemination and impart resistance to immunotherapies. Thus, strategies that convert them into tumor fighters may offer great therapeutic potential. In this study, we evaluated whether pharmacologic modulation of macrophage phenotype by HDAC inhibitors (HDACi) could produce an anti-tumor effect. We demonstrated that low-dose HDACi trichostatin-A (TSA) markedly reshaped the tumor immune microenvironment by modulating the suppressive activity of infiltrating macrophages and inhibiting the recruitment of MDSCs in various tumors. These actions, in turn, augmented anti-tumor immune responses and further enhanced anti-tumor effects of immunotherapies. HDAC inhibition, however, also upregulated PD-L1, thereby limiting the beneficial therapeutic effects. Indeed, combining low-dose TSA with anti-PD-L1 in this model significantly enhanced the durability of tumor reduction and prolonged survival of tumor-bearing mice, compared with the effect of either treatment alone. These data introduce HDAC inhibition as a potential means to harness the anti-tumor potential of macrophages in cancer therapy.
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Registered trials
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.