PD-1 blockade does not enhance alloimmunization after allogeneic dendritic cell vaccination in cancer patients
Frontiers in Immunology, vol. 17, pp. 1763434
Abstract
Background: Blocking programmed cell death protein 1 (PD-1) has become a standard cancer immunotherapy, increasingly used in kidney, liver, or heart transplant recipients who develop skin cancer or hepatocellular carcinoma, despite the increased risk of graft failure or rejection. The mechanism of action of PD-1 blockade relies on stimulating CD8+ T cell activity, but its impact on humoral immunity in general and on alloimmunization in particular remains uncertain. Objective: The aim of this study was to investigate the impact on anti-PD-1 treatment on alloimmunization. Methods: The effect of anti-PD-1 treatment on the generation of anti-HLA (Human Leucocyte Antigen) antibodies was investigated in 72 patients with non-small cell lung cancer vaccinated with an allogeneic plasmacytoid dendritic cell line (PDC*line; six weekly injections), with or without pembrolizumab administered every three weeks. The kinetics and functionality of the anti-HLA generated were analyzed. Results: The results show that 51.4% of the patients developed anti-HLA antibodies, primarily dependent on the vaccine dose. In 60% of cases, the antibody response appeared after the sixth injection, peaked after one month, and then gradually declined over two years. Anti-HLA class II antibodies appeared earlier than class I antibodies. Functional assays demonstrated complement-dependent cytotoxicity against allogeneic B lymphocytes and PDC*line cells in the serum of some patients, with no difference related to treatment. PD-1 blockade did not alter the magnitude, kinetics, or cytotoxic potential of the vaccine-induced humoral response. Conclusion: These results indicate that, during allogeneic human vaccination, PD-1 signaling exerts a limited effect on antibody production and effector function, suggesting a more complex regulatory role in humoral immunity than previously thought.
Authors 27
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Affiliation as printed
R&D Department, PDC*line Pharma France
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Affiliation as printed
R&D Department, PDC*line Pharma France
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Affiliation as printed
G.M. Consultant Company
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Affiliation as printed
R&D Department, PDC*line Pharma France
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Affiliation as printed
R&D Department, PDC*line Pharma France
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Affiliation as printed
R&D and Clinical Departments, PDC*line Pharma Belgique
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Affiliation as printed
Pulmonary Diseases, AZ Delta Campus Rumbeke
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Affiliation as printed
Pulmonology and Thoracic Oncology Department, Jessa Hospital
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Centre Hospitalier Universitaire de Nantes · Nantes Université
Affiliation as printed
Medical Oncology Department, Nantes University Hospital
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Universitair Ziekenhuis Leuven
Affiliation as printed
Respiratory Oncology Unit (Pulmonology), University Hospitals Leuven
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Leiden University Medical Center
Affiliation as printed
Department of Pulmonology, Leiden University Medical Center
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Centre Hospitalier Universitaire de Liège
Affiliation as printed
Department of Pulmonology, Centre Hospitalier Universitaire de Liège
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Affiliation as printed
Pneumology Department, Grand Hôpital de Charleroi, Site Notre Dame
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Affiliation as printed
Medical Oncology Department, Centre Léon Bérard
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The Netherlands Cancer Institute
Affiliation as printed
Thoracic Oncology Department, Netherlands Cancer Institute
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Affiliation as printed
Pulmonology, Jeroen Bosch Hospital
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Affiliation as printed
Clinical Study Centre, Vitaz campus Sint-Niklaas Moerland
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Affiliation as printed
Hematology and Oncology Department, Kliniken der Stadt Koln gGmbH
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Goethe University Frankfurt · University Hospital Frankfurt
Affiliation as printed
Hemato-Oncology Department, Universitätsklinikum Frankfurt (Johannes-Wolfgang Goethe-Universität)
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Affiliation as printed
Pulmonology: Thoracic Oncology, AZ Groeninge, Campus Kennedylaan
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Centre Hospitalier Universitaire de Grenoble
Affiliation as printed
Thoracic Oncology, Service d'Hospitalo-Universitaire de Pneumologie et Pneumo-Oncologie (SHUPP), Centre Hospitalier Universitaire (CHU) Grenoble-Alpes
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Affiliation as printed
R&D and Clinical Departments, PDC*line Pharma Belgique
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Laurence Chaperot corresponding
Centre National de la Recherche Scientifique · Inserm · Établissement Français du Sang · Institut pour l'avancée des biosciences · Université Grenoble Alpes
Affiliation as printed
Recherche et Développement, Etablissement Français du Sang Auvergne-Rhône-Alpes
Université Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences (IAB), team Translational Immunology and Immunotherapy in Chronic Disease
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Centre National de la Recherche Scientifique · Inserm · Établissement Français du Sang · Institut pour l'avancée des biosciences · Université Grenoble Alpes
Affiliation as printed
Recherche et Développement, Etablissement Français du Sang Auvergne-Rhône-Alpes
Université Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences (IAB), team Translational Immunology and Immunotherapy in Chronic Disease
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Affiliation as printed
Department of Oncology and Radiotherapy, Medical University of Gdańsk
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Universitair Ziekenhuis Leuven
Affiliation as printed
Respiratory Oncology Unit (Pulmonology), University Hospitals Leuven
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Affiliation as printed
R&D Department, PDC*line Pharma France
R&D and Clinical Departments, PDC*line Pharma Belgique
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