Trial reportJournal for immunotherapy of cancer2019
Baseline T cell dysfunction by single cell network profiling in metastatic breast cancer patients.
Trial report in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01401062 (Fresolimumab and Radiotherapy in Metastatic Breast Cancer), which is not on this map. Cited by 42 papers.
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.
Fresolimumab and Radiotherapy in Metastatic Breast Cancer
Who cites it
42 citing papers in PubMed, 53 citations in OpenAlex.
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Targeting Matrix Stiffness and Mechanotransduction in Breast Cancer: Implications for Emerging Therapies.International journal of molecular sciences · 2026Review
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Review
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- Exploring the Therapeutic Potential of TGF-β Inhibitors for Liver Fibrosis: Targeting Multiple Signaling Pathways.Journal of clinical and translational hepatology · 2025Review
- Shifting Shapes: The Endothelial-to-Mesenchymal Transition as a Driver for Cancer Progression.International journal of molecular sciences · 2025Review
- From Pathophysiology to Practice: Evolving Pharmacological Therapies, Clinical Complications, and Pharmacogenetic Considerations in Portal Hypertension.Metabolites · 2025Review
- Differential TGF-β1/SMAD4 Signaling Regulates PMN-MDSC Differentiation and Reshapes the Immune Microenvironment in Breast Cancer.Breast cancer (Dove Medical Press) · 2025Article
- Cold and hot tumors: from molecular mechanisms to targeted therapy.Signal transduction and targeted therapy · 2024Review
- Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment.International journal of molecular sciences · 2024Review
- Deciphering MOSPD1's impact on breast cancer progression and therapeutic response.Biology direct · 2024Article
- Molecular and transcriptional basis of bidirectional CD4MedComm · 2024Article
- The breast cancer tumor microenvironment and precision medicine: immunogenicity and conditions favoring response to immunotherapy.Journal of the National Cancer Center · 2024Review
- Investigating tumor immunogenicity in breast cancer: deciphering the tumor immune response to enhance therapeutic approaches.Frontiers in immunology · 2024Review
- Mechanobiological Strategies to Augment Cancer Treatment.ACS omega · 2023Review
- Identification of KIFC1 as an independent prognostic marker in renal clear cell carcinoma correlates with tumor proliferation and immune infiltration.Scientific reports · 2023Article
- The role of CD4MedComm · 2023Review
- ERK Inhibition Promotes Engraftment of Allografts by Reprogramming T-Cell Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Emerging Therapeutic Targets for Portal Hypertension.Current hepatology reports · 2023Review
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 5 institutions in 1 country.
Funding
Abstract
backgroundWe previously reported the results of a multicentric prospective randomized trial of chemo-refractory metastatic breast cancer patients testing the efficacy of two doses of TGFβ blockade during radiotherapy. Despite a lack of objective responses to the combination, patients who received a higher dose of TGFβ blocking antibody fresolimumab had a better overall survival when compared to those assigned to lower dose (hazard ratio of 2.73, p = 0.039). They also demonstrated an improved peripheral blood mononuclear cell (PBMC) counts and increase in the CD8 central memory pool. We performed additional analysis on residual PBMC using single cell network profiling (SCNP).
methodsThe original trial randomized metastatic breast cancer patients to either 1 or 10 mg/kg of fresolimumab, every 3 weeks for 5 cycles, combined with radiotherapy to a metastatic site at week 1 and 7 (22.5 Gy given in 3 doses of 7.5 Gy). Trial immune monitoring results were previously reported. In 15 patients with available residual blood samples, additional functional studies were performed, and compared with data obtained in parallel from seven healthy female donors (HD): SCNP was applied to analyze T cell receptor (TCR) modulated signaling via CD3 and CD28 crosslinking and measurement of evoked phosphorylation of AKT and ERK in CD4 and CD8 T cell subsets defined by PD-1 expression.
resultsAt baseline, a significantly higher level of expression (p < 0.05) of PD-L1 was identified in patient monocytes compared to HD. TCR modulation revealed dysfunction of circulating T-cells in patient baseline samples as compared to HD, and this was more pronounced in PD-1
conclusionsFunctional T cell analysis suggests that baseline T cell functionality is hampered in metastatic breast cancer patients, at least in part mediated by the PD-1 signaling pathway. These preliminary data support the rationale for investigating the possible beneficial effects of adding PD-1 blockade to improve responses to TGFβ blockade and radiotherapy.
trial registrationNCT01401062 .
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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.