title: Recombinant human IL-15 trans-presentation by B leukemic cells from chronic lymphocytic leukemia induces autologous NK cell proliferation leading to improved anti-CD20 immunotherapy.
abstract: Recombinant human IL-15 (rhIL-15) is one of the most promising cytokines for antitumor immunotherapy. In physiology IL-15 trans-presentation by accessory cells leads to pleiotropic activities, including activation of immune cells, such as NK cells. NK cells are largely involved in Ab-dependent cellular cytotoxicity mediated by therapeutic mAbs, such as rituximab, in chronic lymphocytic leukemia (CLL). Nevertheless, in CLL, Ab-dependent cellular cytotoxicity is relatively impaired by the low E:T ratio (NK/B leukemic cells). Thus, any strategy leading to an increase in NK cell number and activation status can offer new strategies for CLL treatment. To this end, we evaluated the effect of rhIL-15 on autologous NK cell stimulation in CLL samples. We show that rhIL-15 induces NK cell activation and proliferation, leading to improved B leukemic cell depletion. This phenomenon is significantly increased in the presence of anti-CD20 mAbs. In addition, the greater effect of obinutuzumab versus rituximab suggests a cooperative role between rhIL-15 signaling and CD16 signaling in the induction of NK cell proliferation. Moreover, rhIL-15-induced proliferation of autologous NK cells is strictly dependent on their interaction with B leukemic cells, identified in this study as new accessory cells for rhIL-15 trans-presentation. Thus, rhIL-15 is able to promote NK cell-based activity in Ab immunotherapy of CLL.
authors.affiliation: INSERM Unité Mixte de Recherche 1037, Cancer Research Center of Toulouse, BP3028 Centre Hospitalier de l'Université Purpan, F-31300 Toulouse, France;
authors.forename: Emilie
authors.initials: E
authors.lastname: Laprevotte
authors.forename: Gregory
authors.initials: G
authors.lastname: Voisin
authors.forename: Loïc
authors.initials: L
authors.lastname: Ysebaert
authors.forename: Christian
authors.initials: C
authors.lastname: Klein
authors.forename: Camille
authors.initials: C
authors.lastname: Daugrois
authors.forename: Guy
authors.initials: G
authors.lastname: Laurent
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournie
authors.forename: Anne
authors.initials: A
authors.lastname: Quillet-Mary
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007167:Immunotherapy; D019409:Interleukin-15 / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D019409:Interleukin-15; D017452:Receptors, IgG; D011994:Recombinant Proteins; D000069283:Rituximab