Pre-existing TGF-β-specific T-cell immunity in patients with pancreatic cancer predicts survival after checkpoint inhibitors combined with radiotherapy

• DOI: 10.1136/jitc-2022-006432
• Publication Date: 2023-03-22T14:32:40Z
• Authors: Rasmus Erik Johan...; Morten Orebo Holm...; Thomas Landkildeh...; Jane P Hasselby; Gro L Willemoe; Özcan Met; Inge Marie Svane; Julia Johansen; Dorte L Nielsen; Inna M Chen; Mads Hald Andersen
• Keywords: Immunity, Cellular; T-Lymphocytes; Vaccination; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Basic Tumor Immunology; Cancer Vaccines; 3. Good health; Pancreatic Neoplasms; Epitopes; Transforming Growth Factor beta; Vaccines, Subunit; Leukocytes, Mononuclear; Tumor Microenvironment; Humans; Immunotherapy; Antigens; Immune Checkpoint Inhibitors; RC254-282

Circulating transforming growth factor-β (TGF-β)-specific T cells that recognize TGF-β-expressing immune regulatory have been described in patients with cancer. TGF-β-derived peptide vaccination modulates the tumor microenvironment and has shown clinical effects animal models of pancreatic cancer (PC). are especially elevated PC may prevent response to checkpoint inhibitors (ICIs). Thus, present study we investigated significance TGF-β-specific T-cell immunity treated ICI combined radiotherapy a randomized phase 2 (CheckPAC).Immune responses epitope entitled TGF-β-15 as well epitopes from Clostridium tetani (tetanus) influenza were measured peripheral blood mononuclear (PBMCs) interferon-ɣ enzyme-linked immunospot assays. PBMCs isolated before after treatment. Correlations between data evaluated parametric non-parametric statistical methods. Survival was analyzed univariate multivariate Cox-regression. specific expanded examined for recognition autologous by flow cytometry.PBMCs 32 TGF-β-15. Patients strong at treatment initiation had longer progression-free overall survival, compared weak or no response. This remained significant analysis. displayed similar towards viral antigens. Furthermore, show responder specifically reacted lysed autologous, cells. Finally, mimicking vaccination, showed repeated stimulations vitro enhanced TGF-β-15.A associated benefit improved survival ICI/radiotherapy PC. Importantly, lack some not caused general dysfunction. recognized could be introduced without spontaneous responses. Taken together, our suggest combining TGF-β-based will beneficial