ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Upregulation of C/EBPα Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Patients with Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 73 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A First-in-Human, Multi-centre, Open-label, Phase 1a/b Clinical Study With RNA Oligonucleotide Drug MTL-CEBPA to Investigate Its Safety, Tolerability, and Antitumour Activity in Patients With Advanced Liver Cancer
An Open Label Phase 1a/b Study of MTL-CEBPA in Combination With a PD-1 Inhibitor (Pembrolizumab) in Adult Patients With Advanced Solid Tumours
Who cites it
73 citing papers in PubMed, 86 citations in OpenAlex.
- The anti-CD33 antibody drug conjugate gemtuzumab ozogamicin depletes and functionally resets CD33+ myeloid-derived suppressor cells in patients with metastatic cancer: a phase 2 single-arm, open-label trial.Journal of leukocyte biology · 2026Trial
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Myeloid-derived suppressor cells in cancer: biology, regulatory networks and theranostic prospects.Signal transduction and targeted therapy · 2026Review
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- Metabolic Regulation of Immune Responses: Molecular Mechanisms, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Mechanisms and reversal strategies of liver fibrosis: from regulation of cell fate to clinical translation.Journal of translational medicine · 2026Review
- PMN-MDSCs-derived exosomal S100A9 drives breast cancer progression by enhancing cancer stemness and CXCL5-mediated metastatic potential.Cell death discovery · 2026Article
- Harnessing myeloid cell plasticity for cancer therapy.Nature cancer · 2026Review
- Glyphosate-Induced Metabolic and Immune Modulation in Hepatoma Cells: Identification of Key Genes as Diagnostic and Therapeutic Targets Using an In Silico Systems Biology Approach.Journal of xenobiotics · 2026Article
- A simple and rapid method for generating antibodies against bovine alphaherpesvirus 1 viral proteins through immunization with virus-infected murine cells.Biochemistry and biophysics reports · 2026Article
- Molecular mechanisms of tumor-associated macrophages in hepatocellular carcinoma development and therapy.World journal of gastroenterology · 2026Review
- RNA activation as a precision dosing modality: MTL-CEBPA for controlled enzyme elevation in MPS I-H.Frontiers in medicine · 2026Article
- Prevalence of gastrointestinal side effects in hepatocellular carcinoma patients receiving sorafenib: a meta-analysis of 136 studies and 14,416 patients.Therapeutic advances in medical oncology · 2026Article
- Systemic MyoAAV-saRNA delivery activates endogenous utrophin and rescues dystrophic pathology in mdx mice.Regenerative therapy · 2025Article
- Immunological Landscape and Molecular Therapeutic Targets of the Tumor Microenvironment in Hepatocellular Carcinoma.International journal of molecular sciences · 2025Review
- Target neutrophil heterogeneity and plasticity in cancer.Journal of hematology & oncology · 2025Review
- A review of C/EBP α: a potential novel target for solid tumor intervention.Journal of translational medicine · 2025Review
- Advances and challenges of targeting epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT).Cardiovascular diabetology · 2025Review
- RNAa: Mechanisms, therapeutic potential, and clinical progress.Molecular therapy. Nucleic acids · 2025Review
- Clinical applications of oligonucleotides for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
13 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
31 authors at 13 institutions in 5 countries.
Funding
Abstract
purposeTo evaluate the mechanisms of how therapeutic upregulation of the transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPα), prevents tumor progression in patients with advanced hepatocellular carcinoma (HCC) and in different mouse tumor models. EXPERIMENTAL
designWe conducted a phase I trial in 36 patients with HCC (NCT02716012) who received sorafenib as part of their standard care, and were given therapeutic C/EBPα small activating RNA (saRNA; MTL-CEBPA) as either neoadjuvant or adjuvant treatment. In the preclinical setting, the effects of MTL-CEBPA were assessed in several mouse models, including BNL-1ME liver cancer, Lewis lung carcinoma (LLC), and colon adenocarcinoma (MC38).
resultsMTL-CEBPA treatment caused radiologic regression of tumors in 26.7% of HCC patients with an underlying viral etiology with 3 complete responders. MTL-CEBPA treatment in those patients caused a marked decrease in peripheral blood monocytic myeloid-derived suppressor cell (M-MDSC) numbers and an overall reduction in the numbers of protumoral M2 tumor-associated macrophages (TAM). Gene and protein analysis of patient leukocytes following treatment showed CEBPA activation affected regulation of factors involved in immune-suppressive activity. To corroborate this observation, treatment of all the mouse tumor models with MTL-CEBPA led to a reversal in the suppressive activity of M-MDSCs and TAMs, but not polymorphonuclear MDSCs (PMN-MDSC). The antitumor effects of MTL-CEBPA in these tumor models showed dependency on T cells. This was accentuated when MTL-CEBPA was combined with checkpoint inhibitors or with PMN-MDSC-targeted immunotherapy.
conclusionsThis report demonstrates that therapeutic upregulation of the transcription factor C/EBPα causes inactivation of immune-suppressive myeloid cells with potent antitumor responses across different tumor models and in cancer patients. MTL-CEBPA is currently being investigated in combination with pembrolizumab in a phase I/Ib multicenter clinical study (NCT04105335).
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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.