title: NK Cell Activation in the Antitumor Response Induced by IFN-α Dendritic Cells Loaded with Apoptotic Cells from Follicular Lymphoma Patients.
abstract: Follicular lymphoma (FL) is the most common form of indolent non-Hodgkin lymphoma. This malignancy is considered virtually incurable, with high response rates to therapy but frequent relapses. We investigated the ability of monocyte-derived dendritic cells generated in the presence of IFN-α and GM-CSF (IFN-DC) and loaded with apoptotic lymphoma cells to activate immune responses against FL cells, with the ultimate goal of designing novel patient-specific vaccination strategies for the treatment of FL. In this article, we show that apoptotic tumor cell-loaded IFN-DC from FL patients, which were cultured for 2 wk with autologous lymphocytes, led to Th1 response skewing, based on significantly higher levels of IFN-γ production and a remarkable increase in CD8(+) and NK cell frequency, consistent with the detection of enhanced cytotoxic effector function toward autologous FL cells. IFN-DC were found to promote efficient NK cell activation, increased expression of cytotoxicity receptors, and extensive IFN-γ production in the virtual absence of IL-10. Moreover, direct recognition and killing of primary autologous lymphoma cells by activated NK cells from FL patients was also demonstrated. A critical role was demonstrated for MHC class I-related chain A and B and membrane-bound IL-15 in IFN-DC-mediated NK cell activation and early IFN-γ production. The overall results indicate that IFN-DC loaded with autologous apoptotic FL cells represent a valuable tool for improving the potency of therapeutic cancer vaccines through the efficient induction of NK cell activation and promotion of CD8(+) T cell antitumor immunity.
authors.affiliation: Reparto di Immunoterapia Sperimentale, Dipartimento di Ematologia, Oncologia e Medicina Sperimentale, Istituto Superiore di Sanità, 00161 Rome, Italy;
authors.forename: Caterina
authors.initials: C
authors.lastname: Lapenta
authors.affiliation: Reparto di Immunoterapia Sperimentale, Dipartimento di Ematologia, Oncologia e Medicina Sperimentale, Istituto Superiore di Sanità, 00161 Rome, Italy;
authors.forename: Simona
authors.initials: S
authors.lastname: Donati
authors.affiliation: Reparto di Immunoterapia Sperimentale, Dipartimento di Ematologia, Oncologia e Medicina Sperimentale, Istituto Superiore di Sanità, 00161 Rome, Italy;
authors.forename: Francesca
authors.initials: F
authors.lastname: Spadaro
authors.affiliation: Unità di Chirurgia Generale, Azienda Ospedaliera Sant'Andrea, Università La Sapienza, 00189 Rome, Italy; and.
authors.forename: Paolo
authors.initials: P
authors.lastname: Castaldo
authors.affiliation: Reparto di Immunoterapia Sperimentale, Dipartimento di Ematologia, Oncologia e Medicina Sperimentale, Istituto Superiore di Sanità, 00161 Rome, Italy;
authors.forename: Filippo
authors.initials: F
authors.lastname: Belardelli
authors.affiliation: Unità di Ematologia, Azienda Ospedaliera Sant'Andrea, Università La Sapienza, 00189 Rome, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Cox
authors.affiliation: Reparto di Immunoterapia Sperimentale, Dipartimento di Ematologia, Oncologia e Medicina Sperimentale, Istituto Superiore di Sanità, 00161 Rome, Italy; stefano.santini@iss.it.
authors.forename: Stefano M
authors.initials: SM
authors.lastname: Santini
mesh_terms: D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000276:immunology*; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008224:Lymphoma, Follicular; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines; D016898:Interferon-alpha