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Publications

Journal Article Epublish

PubMed: 41859082 DOI: 10.3389/fimmu.2026.1763434

PD-1 blockade does not enhance alloimmunization after allogeneic dendritic cell vaccination in cancer patients.

Front Immunol 17:1763434

Authors: Severine Planel, Guillaume Vayssière, Gianni Maggipinto, Estelle Leplus, Karine Laulagnier, Florence Renard, Francoise Myster, Marie Gerard, Ingel Demedts, Kristof Cuppens, Elvire Pons-Tostivint, Els Wauters, Frank J Borm, Anne Sibille, Benoît Colinet, Maurice Pérol, Willemijn S M E Theelen, Bonne Biesma, Charlotte Van De Kerkhove, Eva Buchmeier, Friederike C Althoff, Sofie Derijcke, Denis Moro-Sibilot, Frédérique Cantero, Laurence Chaperot, Philippe Saas, Marcin Skrzypski, Johan Vansteenkiste, Joël Plumas

Affiliations

  • R&D Department, PDC*line Pharma France, Grenoble, France.
  • G.M. Consultant Company, Liège, Belgium.
  • R&D and Clinical Departments, PDC*line Pharma Belgique, Liège, Belgium.
  • Human Leukocyte Antigen (HLA) Laboratory, Etablissement Français du Sang (EFS) Rhone-Alpes Auvergne, Grenoble, France.
  • Pulmonary Diseases, AZ Delta Campus Rumbeke, Roeselare, Belgium.
  • Pulmonology and Thoracic Oncology Department, Jessa Hospital, Hasselt, Belgium.
  • Medical Oncology Department, Nantes University Hospital, Nantes, France.
  • Respiratory Oncology Unit (Pulmonology), University Hospitals Leuven, Leuven, Belgium.
  • Department of Pulmonology, Leiden University Medical Center, Leiden, Netherlands.
  • Department of Pulmonology, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
  • Pneumology Department, Grand Hôpital de Charleroi, Site Notre Dame, Charleroi, Belgium.
  • Medical Oncology Department, Centre Léon Bérard, Lyon, France.
  • Thoracic Oncology Department, Netherlands Cancer Institute, Amsterdam, Netherlands.
  • Pulmonology, Jeroen Bosch Hospital, 's-Hertogenbosch, Netherlands.
  • Clinical Study Centre, Vitaz campus Sint-Niklaas Moerland, Sint-Niklaas, Belgium.
  • Hematology and Oncology Department, Kliniken der Stadt Koln gGmbH, Köln, Germany.
  • Hemato-Oncology Department, Universitätsklinikum Frankfurt (Johannes-Wolfgang Goethe-Universität), Frankfurt Am Main, Germany.
  • Pulmonology: Thoracic Oncology, AZ Groeninge, Campus Kennedylaan, Kortrijk, Belgium.
  • Thoracic Oncology, Service d'Hospitalo-Universitaire de Pneumologie et Pneumo-Oncologie (SHUPP), Centre Hospitalier Universitaire (CHU) Grenoble-Alpes, Grenoble, France.
  • Université Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences (IAB), team Translational Immunology and Immunotherapy in Chronic Disease, Grenoble, France.
  • Recherche et Développement, Etablissement Français du Sang Auvergne-Rhône-Alpes, Grenoble, France.
  • Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.

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.

MeSH

Injections, Immunity, Humoral, Cells, Antibody Formation, Vaccines, Antibodies, Translational Research, Biomedical, Neoplasms, Immunotherapy, Vaccination, Immune System Diseases, Immunity, Transplants, Therapeutics, Dendritic Cells, Cancer Vaccines