1. Reduced frequency of cytotoxic CD56dim CD16+ NK cells leads to impaired antibody-dependent degranulation in EBV-positive classical Hodgkin lymphoma
- Author
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Julien Lazarovici, Tarik Azzi, Philippe Busson, Christian Münz, Elena Pánisová, Juliane Mietz, Monika Kotur, David Ghez, Meike Kaulfuss, Simone Bürgler, Obinna Chijioke, Alina Danu, Christoph Berger, Anna Lünemann, University of Zurich, Azzi, Tarik, Institut Gustave Roussy (IGR), Université Paris-Saclay, Aspects métaboliques et systémiques de l'oncogénèse pour de nouvelles approches thérapeutiques (METSY), and Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Male ,Cancer Research ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,medicine.disease_cause ,10263 Institute of Experimental Immunology ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,hemic and lymphatic diseases ,polycyclic compounds ,Immunology and Allergy ,Medicine ,Cytotoxic T cell ,Antibody-dependent cellular cytotoxicity ,1306 Cancer Research ,Lymphocytes ,Prospective Studies ,Antibody-dependent cell-mediated cytotoxicity ,0303 health sciences ,biology ,Lymphoblast ,Degranulation ,food and beverages ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Middle Aged ,Hodgkin Disease ,CD56 Antigen ,3. Good health ,Killer Cells, Natural ,Phenotype ,Oncology ,030220 oncology & carcinogenesis ,2723 Immunology and Allergy ,Natural killer cells ,Original Article ,Female ,2730 Oncology ,Immunotherapy ,Antibody ,Rituximab ,Adult ,Immunology ,Classical Hodgkin lymphoma ,Antineoplastic Agents ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,610 Medicine & health ,Human leukocyte antigen ,macromolecular substances ,In Vitro Techniques ,GPI-Linked Proteins ,Antibodies ,03 medical and health sciences ,Lysosomal-Associated Membrane Protein 1 ,Humans ,Epstein-Barr virus ,030304 developmental biology ,Aged ,2403 Immunology ,business.industry ,Receptors, IgG ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,Epstein–Barr virus ,10036 Medical Clinic ,Adjunctive treatment ,biology.protein ,Leukocytes, Mononuclear ,570 Life sciences ,business - Abstract
Around 30–50% of classical Hodgkin lymphoma (cHL) cases in immunocompetent individuals from industrialized countries are associated with the B-lymphotropic Epstein-Barr virus (EBV). Although natural killer (NK) cells exhibit anti-viral and anti-tumoral functions, virtually nothing is known about quantitative and qualitative differences in NK cells in patients with EBV+ cHL vs. EBV- cHL. Here, we prospectively investigated 36 cHL patients without known immune suppression or overt immunodeficiency at diagnosis. All 10 EBV+ cHL patients and 25 out 26 EBV- cHL were seropositive for EBV antibodies, and EBV+ cHL patients presented with higher plasma EBV DNA levels compared to EBV- cHL patients. We show that the CD56dim CD16+ NK cell subset was decreased in frequency in EBV+ cHL patients compared to EBV- cHL patients. This quantitative deficiency translates into an impaired CD56dim NK cell mediated degranulation toward rituximab-coated HLA class 1 negative lymphoblastoid cells in EBV+ compared to EBV- cHL patients. We finally observed a trend to a decrease in the rituximab-associated degranulation and ADCC of in vitro expanded NK cells of EBV+ cHL compared to healthy controls. Our findings may impact on the design of adjunctive treatment targeting antibody-dependent cellular cytotoxicity in EBV+ cHL. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-021-02956-x.
- Published
- 2022