Cytokine Overproduction, T-Cell Activation, and Defective T-Regulatory Functions Promote Nephritis in Systemic Lupus Erythematosus

Lupus nephritis (LN) occurs in more than one-third of patients with systemic lupus erythematosus. Its pathogenesis is mostly attributable to the glomerular deposition of immune complexes and overproduction of T helper- (Th-) 1 cytokines. In this context, the high glomerular expression of IL-12 and IL-18 exerts a major pathogenetic role. These cytokines are locally produced by both macrophages and dendritic cells (DCs) which attract other inflammatory cells leading to maintenance of the kidney inflammation. However, other populations including T-cells and B-cells are integral for the development and worsening of renal damage. T-cells include many pathogenetic subsets, and the activation of Th-17 in keeping with defective T-regulatory (Treg) cell function regards as further event contributing to the glomerular damage. These populations also activate B-cells to produce nephritogenic auto-antibodies. Thus, LN includes a complex pathogenetic mechanism that involves different players and the evaluation of their activity may provide an effective tool for monitoring the onset of the disease

Exosomes in melanoma: A role in tumor progression, metastasis and impaired immune system activity

Exosomes (Exo) are small vesicles produced by melanoma cells and the accessory cells of the tumor microenvironment. They emerge via both classical and direct pathways and actively participate in tumor colonisation of distant tissues. The proteins, nucleic acids, cytokines and growth factors engulfed by Exo are transferred to recipient cells, where they drive numerous functions required for the tumor escape from immune system control and tumor progression. By positively or negatively modulating immune cell properties, Exo provoke immune suppression and, in turn, defective dendritic cell (DC) functions. Together, these effects limit the cytotoxicity of T-cells and expand both T-regulatory and myeloid-derived suppressor populations. They also hinder perforin and granzyme production by natural killer cells. Finally, Exo also control the organotropism of melanoma cells. The distinct phenotypic properties of Exo can be exploited both for diagnostic purposes and in the early identification of melanoma patients likely to respond to immunotherapy. The potential therapeutic application of Exo derived from DCs has been demonstrated in vaccination trials, which showed an increase in anti-melanoma activity with respect to circulating tumor cells. However, additional studies are required before Exo can be effectively used in diagnostic and therapeutic applications in melanoma

CORRIGENDUM to The mechanisms of acute interstitial nephritis in the era of immune checkpoint inhibitors in melanoma

In this article, the authors’ first names and surnames were incorrectly listed in the wrong order. The correct author list is: Marco Tucci, Anna Passarelli, Annalisa Todisco, Francesco Mannavola, Luigia Stefania Stucci, Stella D’Oronzo, Michele Rossini, Marco Taurisano, Loreto Gesualdo and Franco Silvestris

cutaneous metastasis as a primary presentation of a pulmonary enteric adenocarcinoma

Background: Primary pulmonary enteric adenocarcinoma (PEAC) is a rare non-small cell lung cancer subtype sharing morphologic and immunohistochemical features with colorectal adenocarcinoma. Given the frequency of lung metastases in colorectal cancer, the differential diagnosis of PEAC according to routine morphological and immunohistochemical findings may be difficult. Genome sequence by next-generation sequencing has recently introduced new perspectives to better define the diagnosis and tumor sensitivity to treatments, while the rarity of this subtype of cancer still limits the current knowledge of its molecular features and provides no information to address patients to tailored therapies. Methods: We diagnosed a rare case of subcutaneous metastasis as a first symptom of a PEAC. Formalin-fixed paraffin-embedded samples of the primary tumor and subcutaneous metastases were examined by immunohistochemistry, and subsequently by targeted next-generation sequencing analysis. Results: Morphological and immunohistochemical findings suggested a rare case of metastatic pulmonary adenocarcinoma with enteric aspects. Next-generation sequencing analysis performed on both the primary tumor sample and the cutaneous lesion identified two pathogenic variants on CDKN2A and KRAS in both of them. However, the metastasis showed two additional pathogenic mutations located in SMAD4 and FLT3 genes. Conclusions: We describe for the first time an extensive molecular analysis on a rare case of PEAC with an unusual cutaneous metastasis. Our observation suggests that a specific pattern of mutations is harbored in this neoplasm, and that additional molecular studies may provide further information to identify prognostic and hopefully predictive genes of response to treatment

Search for the Standard Model Higgs boson produced by vector-boson fusion and decaying to bottom quarks in √s=8 TeV pp collisions with the ATLAS detector

A search with the ATLAS detector is presented for the Standard Model Higgs boson produced by vector-boson fusion and decaying to a pair of bottom quarks, using 20.2 fb⁻¹ of LHC proton-proton collision data at √s=8 TeV. The signal is searched for as a resonance in the invariant mass distribution of a pair of jets containing b-hadrons in vector-boson-fusion candidate events. The yield is measured to be −0.8 ± 2.3 times the Standard Model cross-section for a Higgs boson mass of 125 GeV. The upper limit on the cross-section times the branching ratio is found to be 4.4 times the Standard Model cross-section at the 95% confidence level, consistent with the expected limit value of 5.4 (5.7) in the background-only (Standard Model production) hypothesis

Dark matter interpretations of ATLAS searches for the electroweak production of supersymmetric particles in √s=8 TeV proton-proton collisions

A selection of searches by the ATLAS experiment at the LHC for the electroweak production of SUSY particles are used to study their impact on the constraints on dark matter candidates. The searches use 20fb⁻¹ of proton-proton collision data at √s=8 TeV. A likelihood-driven scan of a five-dimensional effective model focusing on the gaugino--higgsino and Higgs sector of the phenomenological minimal supersymmetric Standard Model is performed. This scan uses data from direct dark matter detection experiments, the relic dark matter density and precision flavour physics results. Further constraints from the ATLAS Higgs mass measurement and SUSY searches at LEP are also applied. A subset of models selected from this scan are used to assess the impact of the selected ATLAS searches in this five-dimensional parameter space. These ATLAS searches substantially impact those models for which the mass m(χ0/1) of the lightest neutralino is less than 65 GeV, excluding 86% of such models. The searches have limited impact on models with larger m(χ0/1) due to either heavy electroweakinos or compressed mass spectra where the mass splittings between the produced particles and the lightest supersymmetric particle is small

Search for pair production of Higgs bosons in the bbbb final state using proton--proton collisions at √s = 13 TeV with the ATLAS detector

A search for Higgs-boson pair production in the bbbb final state is carried out with 3.2 fb⁻¹ of proton--proton collision data collected at √s=13 TeV with the ATLAS detector. The data are consistent with the estimated background and are used to set upper limits on the production cross section of Higgs-boson pairs times branching ratio to bbbb for both nonresonant and resonant production. In the case of resonant production of Kaluza--Klein gravitons within the Randall--Sundrum model, upper limits in the 24 to 91 fb range are obtained for masses between 600 and 3000 GeV, at the 95% confidence level. The production cross section times branching ratio for nonresonant Higgs-boson pairs is also constrained to be less than 1.22 pb, at the 95% confidence level

Search for high-mass new phenomena in the dilepton final state using proton-proton collisions at √s=13 TeV with the ATLAS detector

A search is conducted for both resonant and non-resonant high-mass new phenomena in dielectron and dimuon final states. The search uses 3.2 fb⁻¹ of proton-proton collision data, collected at √s=13 TeV by the ATLAS experiment at the LHC in 2015. The dilepton invariant mass is used as the discriminating variable. No significant deviation from the Standard Model prediction is observed; therefore limits are set on the signal model parameters of interest at 95% credibility level. Upper limits are set on the cross-section times branching ratio for resonances decaying to dileptons, and the limits are converted into lower limits on the resonance mass, ranging between 2.74 TeV and 3.36 TeV, depending on the model. Lower limits on the ℓℓqq contact interaction scale are set between 16.7 TeV and 25.2 TeV, also depending on the model

Transverse momentum, rapidity, and centrality dependence of inclusive charged-particle production in √sNN=5.02 TeV p + Pb collisions measured by the ATLAS experiment

Measurements of the per-event charged-particle yield as a function of the charged-particle transverse momentum and rapidity are performed using p+ Pb collision data collected by the ATLAS experiment at the LHC at a centre-of-mass energy of √sNN=5.02 TeV. Charged particles are reconstructed over pseudorapidity |η|< 2.3 and transverse momentum between 0.1 GeV and 22 GeV in a dataset corresponding to an integrated luminosity of 1 μb⁻¹. The results are presented in the form of charged-particle nuclear modification factors, where the p+ Pb charged-particle multiplicities are compared between central and peripheral p+ Pb collisions as well as to charged-particle cross sections measured in pp collisions. The p+ Pb collision centrality is characterized by the total transverse energy measured in −4.9 < η < −3.1 , which is in the direction of the outgoing lead beam. Three different estimations of the number of nucleons participating in the p+ Pb collision are carried out using the Glauber model and two Glauber-Gribov colour-fluctuation extensions to the Glauber model. The values of the nuclear modification factors are found to vary significantly as a function of rapidity and transverse momentum. A broad peak is observed for all centralities and rapidities in the nuclear modification factors for charged-particle transverse momentum values around 3 GeV. The magnitude of the peak increases for more central collisions as well as rapidity ranges closer to the direction of the outgoing lead nucleus

Measurement of the bb dijet cross section in pp collisions at √s = 7 TeV with the ATLAS detector

The dijet production cross section for jets containing a b-hadron (b-jets) has been measured in proton–proton collisions with a centre-of-mass energy of √s =7 TeV, using the ATLAS detector at the LHC. The data used correspond to an integrated luminosity of 4.2fb⁻¹. The cross section is measured for events with two identified b-jets with a transverse momentum pT>20GeV and a minimum separation in the η–ϕ plane of ΔR=0.4. At least one of the jets in the event is required to have p T >270 GeV. The cross section is measured differentially as a function of dijet invariant mass, dijet transverse momentum, boost of the dijet system, and the rapidity difference, azimuthal angle and angular distance between the b-jets. The results are compared to different predictions of leading order and next-to-leading order perturbative quantum chromodynamics matrix elements supplemented with models for parton-showers and hadronization