Trial reportJournal for immunotherapy of cancer2023
Pre-existing TGF-β-specific T-cell immunity in patients with pancreatic cancer predicts survival after checkpoint inhibitors combined with radiotherapy.
Trial report in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Impact of Liver Metastases on Outcomes With Chemotherapy or Immune Checkpoint Inhibitors in Pancreatic Cancer.Immunity, inflammation and disease · 2026Observational
- Immune modulatory vaccines targeting tumor microenvironment antigens: recent advances in oncology and beyond.Signal transduction and targeted therapy · 2026Review
- Rationale for multi-epitope TGFβ vaccination in pancreatic cancer: evidence from immunologic and clinical correlates.Signal transduction and targeted therapy · 2026Article
- Five-year clinical outcome and immune biomarkers of durable response from the MM1636 trial on IDO/PD-L1 vaccination and PD-1 blockade in first line metastatic melanoma.Nature communications · 2025Article
- Baseline (modified) Glasgow prognostic score as a predictor of therapeutic response to immune checkpoint inhibitors in solid tumors: A systematic review and meta‑analysis.Oncology letters · 2025Article
- The antitumor activity of TGFβ-specific T cells is dependent on IL-6 signaling.Cellular & molecular immunology · 2025Article
- TGFβ in Pancreas and Colorectal Cancer: Opportunities to Overcome Therapeutic Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- TGFβ-specific T cells induced by a TGFβ-derived immune modulatory vaccine both directly and indirectly modulate the phenotype of tumor-associated macrophages and fibroblasts.Journal for immunotherapy of cancer · 2024Article
- Promoting Articular Cartilage Regeneration through Microenvironmental Regulation.Journal of immunology research · 2024Review
- Pre-existing cell populations with cytotoxic activity against SARS-CoV-2 in people with HIV and normal CD4/CD8 ratio previously unexposed to the virus.Frontiers in immunology · 2024Article
- Radioimmunotherapy: a game-changer for advanced non-small cell lung cancer.Frontiers in immunology · 2024Review
- The Role of the Transforming Growth Factor-β Signaling Pathway in Gastrointestinal Cancers.Biomolecules · 2023Review
- Novel immune modulatory vaccines targeting TGFβ.Cellular & molecular immunology · 2023Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCirculating transforming growth factor-β (TGF-β)-specific T cells that recognize TGF-β-expressing immune regulatory cells have been described in patients with cancer. TGF-β-derived peptide vaccination modulates the tumor microenvironment and has shown clinical effects in animal models of pancreatic cancer (PC). TGF-β-expressing regulatory cells are especially elevated in PC and may prevent the clinical response to immune checkpoint inhibitors (ICIs). Thus, in the present study we investigated the significance of TGF-β-specific T-cell immunity in patients with PC treated with ICI combined with radiotherapy in a randomized phase 2 study (CheckPAC).
methodsImmune responses to a TGF-β-derived epitope entitled TGF-β-15 as well as epitopes from
resultsPBMCs from 32 patients were analyzed for immune responses to the TGF-β-derived epitope entitled TGF-β-15. Patients with a strong TGF-β-specific immune response at treatment initiation had longer progression-free and overall survival, compared with patients with a weak or no TGF-β-specific immune response. This remained significant in multivariate analysis. Patients with weak and strong TGF-β-specific responses displayed similar responses towards viral antigens. Furthermore, we show that TGF-β-specific T cells from a clinical responder specifically reacted to and lysed autologous, regulatory immune cells. Finally, mimicking a TGF-β-15 vaccination, we showed that repeated stimulations with the TGF-β-15 epitope
conclusionA strong TGF-β-15 specific immune response was associated with clinical benefit and improved survival after ICI/radiotherapy for patients with PC. Importantly, the lack of TGF-β-specific T cells in some patients was not caused by a general immune dysfunction. TGF-β-specific T cells recognized regulatory immune cells and could be introduced
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