22 research outputs found

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Measurement of charged particle spectra in minimum-bias events from proton-proton collisions at root s =13 TeV

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    Pseudorapidity, transverse momentum, and multiplicity distributions are measured in the pseudorapidity range vertical bar eta vertical bar 0.5 GeV in proton-proton collisions at a center-of-mass energy of root s = 13 TeV. Measurements are presented in three different event categories. The most inclusive of the categories corresponds to an inelastic pp data set, while the other two categories are exclusive subsets of the inelastic sample that are either enhanced or depleted in single diffractive dissociation events. The measurements are compared to predictions from Monte Carlo event generators used to describe high-energy hadronic interactions in collider and cosmic-ray physics.Peer reviewe

    Search for resonant pair production of Higgs bosons decaying to bottom quark-antiquark pairs in proton-proton collisions at 13 TeV

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    A search for a narrow-width resonance decaying into two Higgs bosons, each decaying into a bottom quark-antiquark pair, is presented. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 35.9 fb−1^{-1} at s=\sqrt{s}= 13 TeV recorded by the CMS detector at the LHC. No evidence for such a signal is observed. Upper limits are set on the product of the production cross section for the resonance and the branching fraction for the selected decay mode in the resonance mass range from 260 to 1200 GeV

    Search for supersymmetric partners of electrons and muons in proton–proton collisions at s=13TeV

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    A search for direct production of the supersymmetric (SUSY) partners of electrons or muons is presented in final states with two opposite-charge, same-flavour leptons (electrons and muons), no jets, and large missing transverse momentum. The data sample corresponds to an integrated luminosity of 35.9 fb−1 of proton–proton collisions at s=13TeV, collected with the CMS detector at the LHC in 2016. The search uses the MT2 variable, which generalises the transverse mass for systems with two invisible objects and provides a discrimination against standard model backgrounds containing W bosons. The observed yields are consistent with the expectations from the standard model. The search is interpreted in the context of simplified SUSY models and probes slepton masses up to approximately 290, 400, and 450 GeV, assuming right-handed only, left-handed only, and both right- and left-handed sleptons (mass degenerate selectrons and smuons), and a massless lightest supersymmetric particle. Limits are also set on selectrons and smuons separately. These limits show an improvement on the existing limits of approximately 150 GeV.0info:eu-repo/semantics/publishe

    Observation of proton-tagged, central (semi)exclusive production of high-mass lepton pairs in pp collisions at 13 TeV with the CMS-TOTEM precision proton spectrometer

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    Evidence for X(3872) in Pb-Pb Collisions and Studies of its Prompt Production at sNN\sqrt {s_{NN}}=5.02 TeV

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    The first evidence for X(3872) production in relativistic heavy ion collisions is reported. The X(3872)X(3872) production is studied in lead-lead (Pb-Pb) collisions at a center-of-mass energy of sNN\sqrt {s_{NN}} 5.02 TeV per nucleon pair, using the decay chain X(3872)→J/ψπ+π−→Ό+Ό−π+π−X(3872) → J/ψ π^+ π^− → ÎŒ^+ ÎŒ^- π^+ π^−. The data were recorded with the CMS detector in 2018 and correspond to an integrated luminosity of 1.7 nb−1^{-1}. The measurement is performed in the rapidity and transverse momentum ranges ∣y∣<|y|< 1.6 and 15<pT< < p_T < 50 GeV/c. The significance of the inclusive X(3872)X(3872) signal is 4.2 standard deviations. The prompt X(3872)X(3872) to ψ2Sψ2S yield ratio is found to be ρPb−Pb=1.08±0.49(stat)±0.52(syst)ρ^{Pb-Pb} =1.08±0.49(stat)±0.52(syst), to be compared with typical values of 0.1 for pp collisions. This result provides a unique experimental input to theoretical models of the X(3872)X(3872) production mechanism, and of the nature of this exotic state
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