15 research outputs found

    PD-1 checkpoint inhibition enhances the antilymphoma activity of CD19-CAR-iNKT cells that retain their ability to prevent alloreactivity.

    Get PDF
    Relapse and graft-versus-host disease (GVHD) are the main causes of death after allogeneic hematopoietic cell transplantation (HCT). Preclinical murine models and clinical data suggest that invariant natural killer T (iNKT) cells prevent acute and chronic GVHD. In addition, iNKT cells are crucial for efficient immune responses against malignancies and contribute to reduced relapse rates after transplantation. Chimeric antigen receptors (CAR) redirect effector cells to cell surface antigens and enhance killing of target cells. With this study, we aimed to combine enhanced cytotoxicity of CD19-CAR-iNKT cells against lymphoma cells with their tolerogenic properties. iNKT cells were isolated from peripheral blood mononuclear cells and transduced with an anti-CD19-CAR retrovirus. After in vitro expansion, the functionality of CD19-CAR-iNKT cells was assessed by flow cytometry, image stream analysis and multiplex analysis in single-stimulation or repeated-stimulation assays. Moreover, the immunoregulatory properties of CD19-CAR-iNKT cells were analyzed in apoptosis assays and in mixed lymphocyte reactions. The effect of checkpoint inhibition through nivolumab was analyzed in these settings. In this study, we could show that the cytotoxicity of CD19-CAR-iNKT cells was mediated either through engagement of their CAR or their invariant T-cell receptor, which may circumvent loss of response through antigen escape. However, encounter of CD19-CAR-iNKT cells with their target induced a phenotype of exhaustion. Consequently, checkpoint inhibition increased cytokine release, cytotoxicity and survival of CD19-CAR-iNKT cells. Additionally, they showed robust suppression of alloreactive immune responses. In this work, we demonstrate that CAR-iNKT cells are a powerful cytotherapeutic option to prevent or treat relapse while potentially reducing the risk of GVHD after allogeneic HCT

    Le coppie miste in Italia: identità e alterità nei nuovi contesti migratori

    No full text
    Le coppie "miste" non costituiscono certo uno specifico oggetto clinico, né una categoria sociologica a sé stante. Tuttavia, se questo tipo di famiglia costituiva nel nostro paese un fenomeno ultra minoritario fino a poco tempo fa, oggi l'incidenza dei matrimoni con almeno un coniuge straniero rappresenta una larga porzione del totale dei matrimoni celebrati in Italia. L'interesse che queste unioni rivestono per la psichiatria transculturale è quindi legato all'emergenza nelle società occidentali di scenari plurilinguistici e sempre più multiculturali, in rapporto con l'ampiezza dei flussi migratori che caratterizzano la nostra epoca. Si descrive il caso clinico di una coppia mista italo-nigeriana

    Analisi della popolazione immigrata afferente al Centro Psico Sociale di Pavia (2006-2009) e confronto con i nuovi dati aggiornati al 30 ottobre 2010

    No full text
    L’obiettivo del nostro studio è stato quello di realizzare un’analisi descrittiva delle caratteristiche demografiche, sociali e cliniche della popolazione immigrata che si è rivolta al Centro Psico Sociale di Pavia tra il 2006 e il 2009. Il nostro sta lavoro sta proseguendo attraverso la raccolta dei dati del 2010 tramite un questionario realizzato dal gruppo “Psichiatria e migrazione”in collaborazione con l’Istituto di Psichiatria dell’università di Bologna

    Letter

    No full text

    Analisi della popolazione immigrata afferente al Centro Psico-Sociale di Pavia (2006-2009): drop out e presa in carico

    No full text
    Scopo dello studio e analizzare la popolazione immigrata afferente al Centro Psico-Sociale di Pavia dal 2006 al 2009; confrontare le caratteristiche cliniche e demografiche dei pazienti in carico e di coloro che hanno sospeso senza preavviso i contatti con i curanti, non ripresentandosi più entro ottobre 2010 (drop out)

    Seasonal fluctuations in problem behaviors among young adults with autism and intellectual disability

    No full text
    BACKGROUND: Acute behavioral alterations have been frequently reported in patients with autism. However, the question as to whether behavioral problems undergo seasonal variations in autism remains to be addressed. MATERIAL/METHODS: In a prospective observational study over 29 months, problem behaviors amongst 23 young adults with autism and intellectual disability living in a farm community center were assessed. Behavioral problems were recorded daily using the Rossago Behavioral Checklist. Data were collected on clinical characteristics, drug usage, changes in staff composition, daily schedule, rehabilitative activities, and food administration. RESULTS: Problem behaviors showed significant seasonal fluctuations. The frequency of problem behaviors showed a maximum in mid-April and a minimum in mid-October (mean difference: 1.24 behaviors). CONCLUSIONS: Taken together, these data suggest the occurrence of significant seasonal fluctuations in problem behaviors amongst young adults with autism and intellectual disability. Further studies are needed to shed more light on the mechanisms underlying these fluctuations
    corecore