ArticleJournal for immunotherapy of cancer2018
Targeting the TGFβ pathway with galunisertib, a TGFβRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint blockade.
Article in Journal for immunotherapy of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 240 papers, 1 of them a synthesis that pooled it.
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Who cites it
240 citing papers in PubMed, 1 synthesis or guideline pooled it, 363 citations in OpenAlex.
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Biomarker Analysis from Patients with Metastatic PDAC Treated with TGFβ Antibody NIS793 plus Abraxane + Gemcitabine versus Abraxane + Gemcitabine Alone in a Phase II, Open-Label, Randomized Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- A phase Ib/II study of galunisertib in combination with nivolumab in solid tumors and non-small cell lung cancer.BMC cancer · 2023Trial
- Dual PD-L1 and TGF-b blockade in patients with recurrent respiratory papillomatosis.Journal for immunotherapy of cancer · 2021Trial
- 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
- Reframing cancer therapy through tumor plasticity.Nature cancer · 2026Review
- Natural Killer Cell Immunotherapy in Solid Tumors: Microenvironmental Obstacles and Translational 3D Models.Biology · 2026Review
- Patient-derived model capturing hypoxia and extracellular matrix remodelling of immunologically cold high-grade serous tumours.Nature communications · 2026Article
- BCR-ABL1 Drives Transcriptional Reprogramming of Chronic Myeloid Leukemia Cells for Immune Evasion Through C/EBPβ.MedComm · 2026Article
- The TGF-βR1 inhibitor galunisertib re-shapes the PDAC-TME by limiting decidual-like natural killer cells polarization.Cell death & disease · 2026Article
- FOXA1 loss drives basal/squamous de-differentiation of prostate cancer and induces an immunosuppressive tumor microenvironment.Nature communications · 2026Article
- Chemoresistance: The hidden barrier in cancer treatment.Cancer pathogenesis and therapy · 2026Review
- Amelioration of colorectal cancer-associated fibroblasts in immunosuppressive microenvironment by ferroptosis-based nanotherapy.Nature communications · 2026Article
- The Significance of the Heterogeneity of Cancer-Associated Fibroblasts in Tumor Microenvironments.Metabolites · 2026Review
- Tumor microenvironment-driven drug resistance in urologic cancers: mechanisms and therapeutic targets.Genes & genomics · 2026Review
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Immune-Centered Cross-Talk Between Cancer Cells and the Tumor Microenvironment-Implications for Therapy.Cancers · 2026Review
- Rapid selection of high-affinity DARPins using click display.Protein engineering, design & selection : PEDS · 2026Article
- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- Oncogene Mutations: The Shared Antigen Vaccines That Work?Annual review of medicine · 2026Review
180 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTGFβ signaling plays a pleotropic role in tumor biology, promoting tumor proliferation, invasion and metastasis, and escape from immune surveillance. Inhibiting TGFβ's immune suppressive effects has become of particular interest as a way to increase the benefit of cancer immunotherapy. Here we utilized preclinical models to explore the impact of the clinical stage TGFβ pathway inhibitor, galunisertib, on anti-tumor immunity at clinically relevant doses.
resultsIn vitro treatment with galunisertib reversed TGFβ and regulatory T cell mediated suppression of human T cell proliferation. In vivo treatment of mice with established 4T1-LP tumors resulted in strong dose-dependent anti-tumor activity with close to 100% inhibition of tumor growth and complete regressions upon cessation of treatment in 50% of animals. This effect was CD8+ T cell dependent, and led to increased T cell numbers in treated tumors. Mice with durable regressions rejected tumor rechallenge, demonstrating the establishment of immunological memory. Consequently, mice that rejected immunogenic 4T1-LP tumors were able to resist rechallenge with poorly immunogenic 4 T1 parental cells, suggesting the development of a secondary immune response via antigen spreading as a consequence of effective tumor targeting. Combination of galunisertib with PD-L1 blockade resulted in improved tumor growth inhibition and complete regressions in colon carcinoma models, demonstrating the potential synergy when cotargeting TGFβ and PD-1/PD-L1 pathways. Combination therapy was associated with enhanced anti-tumor immune related gene expression profile that was accelerated compared to anti-PD-L1 monotherapy.
conclusionsTogether these data highlight the ability of galunisertib to modulate T cell immunity and the therapeutic potential of combining galunisertib with current PD-1/L1 immunotherapy.
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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.