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BACKGROUND AND AIM: Gliadin presentation by HLA-DQ2/8 molecules to T cells plays a crucial role in triggering the inflammatory cascade in coeliac disease. We aimed to study the immunological effects of gliadin stimulation on dendritic cells (DCs) from HLA-DQ8 transgenic and BALB/c mice. METHODS: Bone marrow-derived DCs were stimulated with alpha-chymotrypsin-digested gliadin or ovoalbumin (100mug/ml). Modification of DC maturation, through HLA-DQ8 and MHC class II expression, and activation, by CD80 and CD86, was assessed by flow cytometry. The ability of pulsed and unpulsed DCs to prime T cells was evaluated by mixed leucocyte reaction. The expression of interleukin-4, -10, -12p70 and interferon-alpha, as well as of Toll-like receptor-4, -7, -8, -9 was determined by ELISA and real-time RT-PCR, respectively. RESULTS: Gliadin stimulation induced DC maturation (p

Background Ipilimumab (IPI) has shown long lasting responses in metastatic melanoma (MM) patients (pts) in phase II/III trials (Hodi et al., NEJM 2010; Robert et al. NEJM 2011; Prieto et al., CCR 2012). We have previously reported a significant clinical efficacy of IPI in 27 heavily pre-treated MM pts enrolled within the 10 mgs expanded access program (EAP) available at the University Hospital of Siena; one and 2-years survival were 34.8% and 23.5%, respectively (Di Giacomo, et al. CII, 2010). In spite of its clinical efficacy, no definitive predictive markers of response have been identified yet. We report here the survival follow-up of this cohort of MM pts and preliminary data on immunological correlates. Methods Twenty-seven pts with stage III (2) or IV (25) MM, progressing to a median of 3 (1-5) systemic therapies, were treated according to the EAP with IPI at 10 mg/Kg i.v. given at weeks (wks) 1, 4, 7, 10 during the induction phase, and every 12 wks from W24 in the maintenance phase. Peripheral blood mononuclear cells were collected from 17 pts at baseline, W7, W12 and W24 and analyzed by flow cytometry for ICOS expression on both CD4 and CD8+ T cells. The ratio between absolute blood neutrophils (N) and lymphocytes (L) count was determined at baseline, W4, W7 and W10 for 27, 27, 24 and 23 pts, respectively. Results With a median follow-up of 9.6 months the median OS was 9.6 months (95% CI: 4.2-16.1; range: 3.1-51.2; three and 4-years survival rates were 20.9%, with 5 long-term survivors (>4 yrs). A significant (p Conclusions ipi can induce long-term survivals in heavily pre-treated MM pts. Circulating ICOS+ T cells and N/L ratio in the course of treatment with ipi may represent predictive markers of clinical effectiveness in the daily practice. Disclosure M. Maio: Advisory Board and Honoraria from Bristol-Myers Squibb and Roche. All other authors have declared no conflicts of interest.