ArticleCells2019
Combined Inhibition of TGF-β Signaling and the PD-L1 Immune Checkpoint Is Differentially Effective in Tumor Models.
Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- A phase Ib/II study of galunisertib in combination with nivolumab in solid tumors and non-small cell lung cancer.BMC cancer · 2023Trial
- Safety and activity of the TGFβ receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer.Journal for immunotherapy of cancer · 2021Trial
- Development of a novel immune infiltration-based gene signature to predict prognosis and immunotherapy response of a novel anti-PD-L1/TGF-β bifunctional fusion protein in recurrent cervical cancer.Human vaccines & immunotherapeutics · 2026Article
- Intravenously deliverable oncolytic virus VET3-TGI favorably alters the tumor microenvironment.Journal for immunotherapy of cancer · 2026Article
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Potent antitumor activity through dual targeting of PD-L1 and TGF-β pathways in the glioma tumor microenvironment.Journal for immunotherapy of cancer · 2026Article
- Macrophages in tumors with downregulated MHC-I expression: emerging therapeutic opportunities and translational challenges.Clinical and experimental immunology · 2026Review
- Review
- Immunomodulatory Effects of a New Ethynylpiperidine Derivative: Enhancement of CD4Biomedicines · 2025Article
- Quercetin targets TGFβ-primed human MDA-MB-231 triple-negative breast cancer cells, linking epithelial-mesenchymal transition to cell senescence and fibrosis.Molecular biology reports · 2025Article
- Dynamics of inflammatory signals within the tumor microenvironment.World journal of experimental medicine · 2025Review
- Therapeutic targeting of TGF-β in lung cancer.The FEBS journal · 2025Review
- Targeting TGF-β: a promising strategy for cancer therapy.Medical oncology (Northwood, London, England) · 2025Review
- Structural insights and clinical advances in small-molecule inhibitors targeting TGF-β receptor I.Molecular therapy. Oncology · 2025Review
- Development of a nomogram integrating immune checkpoints, fibrosis indicators, and clinicopathological characteristics to predict overall survival in pancreatic cancer: a retrospective analysis.Frontiers in immunology · 2025Article
- Tumor-intrinsic CDC42BPB confers resistance to anti-PD-1 immune checkpoint blockade in breast cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Review
- Adenosine Increases the Immunosuppressive Capacity of Cervical Cancer Cells by Increasing PD-L1 Expression and TGF-β Production through Its Interaction with APharmaceuticals (Basel, Switzerland) · 2024Article
- Clinical immunotherapy in pancreatic cancer.Cancer immunology, immunotherapy : CII · 2024Review
2 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
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibodies blocking the programmed death-ligand 1 (PD-L1) have shown impressive and durable responses in clinical studies. However, this type of immunotherapy is only effective in a subset of patients and not sufficient for rejection of all tumor types. In this study, we explored in two mouse tumor models whether the antitumor effect could be enhanced by the combined blockade of PD-L1 and transforming growth factor-β (TGF-β), a potent immunosuppressive cytokine. The effect of anti-PD-L1 mouse monoclonal (mAb) and a TGF-β type I receptor small molecule kinase inhibitor (LY364947) was evaluated in the highly immunogenic mouse MC38 colon adenocarcinoma and the poorly immunogenic mouse KPC1 pancreatic tumor model. In the MC38 tumor model, LY364947 monotherapy did not show any antitumor effect, whereas treatment with anti-PD-L1 mAb significantly delayed tumor outgrowth. However, combination therapy showed the strongest therapeutic efficacy, resulting in improved long-term survival compared with anti-PD-L1 mAb monotherapy. This improved survival was associated with an increased influx of CD8⁺ T cells in the tumor microenvironment. In the KPC1 tumor model, LY364947 did not enhance the antitumor effect of anti-PD-L1 mAb. Despite this, delayed KPC1 tumor outgrowth was observed in the LY364947-treated group and this treatment led to a significant reduction of CD4⁺ T cells in the tumor microenvironment. Together, our data indicate that an additive anti-tumor response of dual targeting PD-L1 and TGF-β is dependent on the tumor model used, highlighting the importance of selecting appropriate cancer types, using in-depth analysis of the tumor microenvironment, which can benefit from combinatorial immunotherapy regimens.
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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.