A transcriptionally and functionally distinct PD-1⁺ CD8⁺ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade.

Evidence from mouse chronic viral infection models suggests that CD8 <sup>+</sup> T cell subsets characterized by distinct expression levels of the receptor PD-1 diverge in their state of exhaustion and potential for reinvigoration by PD-1 blockade. However, it remains unknown whether T cells in human cancer adopt a similar spectrum of exhausted states based on PD-1 expression levels. We compared transcriptional, metabolic and functional signatures of intratumoral CD8 <sup>+</sup> T lymphocyte populations with high (PD-1 <sup>T</sup> ), intermediate (PD-1 <sup>N</sup> ) and no PD-1 expression (PD-1 <sup>-</sup> ) from non-small-cell lung cancer patients. PD-1 <sup>T</sup> T cells showed a markedly different transcriptional and metabolic profile from PD-1 <sup>N</sup> and PD-1 <sup>-</sup> lymphocytes, as well as an intrinsically high capacity for tumor recognition. Furthermore, while PD-1 <sup>T</sup> lymphocytes were impaired in classical effector cytokine production, they produced CXCL13, which mediates immune cell recruitment to tertiary lymphoid structures. Strikingly, the presence of PD-1 <sup>T</sup> cells was strongly predictive for both response and survival in a small cohort of non-small-cell lung cancer patients treated with PD-1 blockade. The characterization of a distinct state of tumor-reactive, PD-1-bright lymphocytes in human cancer, which only partially resembles that seen in chronic infection, provides potential avenues for therapeutic intervention

Neoadjuvant treatment does not influence PD-L1 expression in stage III non-small-cell lung cancer: a retrospective analysis of tumor samples from the trials SAKK 16/96, 16/00, 16/01, and 16/14.

The inclusion of immune checkpoint inhibitors (ICIs) in the treatment of operable stage III non-small-cell lung cancer is becoming a new standard. Programmed death-ligand 1 (PD-L1) protein expression on tumor cells has emerged as the most important biomarker for sensitivity to ICIs targeting the programmed cell death protein 1 (PD-1)-PD-L1 axis. Little is known about the impact of neoadjuvant treatment on PD-L1 expression. We assessed PD-L1 expression by immunohistochemistry (Ventana SP263 assay) on tumor cells in treatment-naive diagnostic tumor samples and matched lung resections from patients with stage III non-small-cell lung cancer included in the Swiss Group for Clinical Cancer Research (SAKK) trials 16/96, 16/00, 16/01, and 16/14. All patients received neoadjuvant chemotherapy (CT) with cisplatin/docetaxel, either as single modality (CT), with sequential radiotherapy [chemoradiation therapy (CRT)] or with the PD-L1 inhibitor durvalumab (CT + ICI). Overall, 132 paired tumor samples were analyzed from patients with neoadjuvant CT (n = 69), CRT (n = 33) and CT + ICI (n = 30). For CT and CRT, PD-L1 expression before and after neoadjuvant treatment did not differ significantly (Wilcoxon test, P = 0.94). Likewise, no statistically significant difference was observed between CT and CRT for PD-L1 expression after neoadjuvant treatment (P = 0.97). For CT + ICI, PD-L1 expression before and after neoadjuvant treatment also did not differ significantly (Wilcoxon test, P > 0.99). Event-free survival and overall survival for patients with downregulation or upregulation of PD-L1 expression after neoadjuvant treatment were similar. In our cohort of patients neoadjuvant treatment did not influence PD-L1 expression, irrespective of the specific neoadjuvant treatment protocol. Dynamic change of PD-L1 expression did not correlate with event-free survival or overall survival

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for direct stau production in events with two hadronic tau-leptons in root s=13 TeV pp collisions with the ATLAS detector

A search for the direct production of the supersymmetric partners ofτ-leptons (staus) in final stateswith two hadronically decayingτ-leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of139fb−1, recorded with the ATLAS detector at the LargeHadron Collider at a center-of-mass energy of 13 TeV. No significant deviation from the expected StandardModel background is observed. Limits are derived in scenarios of direct production of stau pairs with eachstau decaying into the stable lightest neutralino and oneτ-lepton in simplified models where the two staumass eigenstates are degenerate. Stau masses from 120 GeV to 390 GeV are excluded at 95% confidencelevel for a massless lightest neutralino

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe

Search for additional heavy neutral Higgs and gauge bosons in the ditau final state produced in 36 fb−1 of pp collisions at √s=13 TeV with the ATLAS detector

A search for heavy neutral Higgs bosons and Z′ bosons is performed using a data sample corresponding to an integrated luminosity of 36.1 fb−1 from proton-proton collisions at √s=13 TeV recorded by the ATLAS detector at the LHC during 2015 and 2016. The heavy resonance is assumed to decay to τ+τ− with at least one tau lepton decaying to final states with hadrons and a neutrino. The search is performed in the mass range of 0.2-2.25 TeV for Higgs bosons and 0.2-4.0 TeV for Z′ bosons. The data are in good agreement with the background predicted by the Standard Model. The results are interpreted in benchmark scenarios. In the context of the hMSSM scenario, the data exclude tan β > 1.0 for mA= 0.25 TeV and tan β > 42 for mA=1.5 TeV at the 95% confidence level. For the Sequential Standard Model, ZSSM′ with mZ′< 2.42 TeV is excluded at 95% confidence level, while Z NU′ with mZ ′ < 2.25 TeV is excluded for the non-universal G(221) model that exhibits enhanced couplings to third-generation fermions

Search for doubly charged Higgs boson production in multi-lepton final states with the ATLAS detector using proton-proton collisions at √s = 13TeV

A search for doubly charged Higgs bosons with pairs of prompt, isolated, highly energetic leptons with the same electric charge is presented. The search uses a proton–proton collision data sample at a centre-of-mass energy of 13 TeV corresponding to 36.1 fb −1 of integrated luminosity recorded in 2015 and 2016 by the ATLAS detector at the LHC. This analysis focuses on the decays H±±→e±e±, H±±→e±μ± and H±±→μ±μ±, fitting the dilepton mass spectra in several exclusive signal regions. No significant evidence of a signal is observed and corresponding limits on the production cross-section and consequently a lower limit on m(H±±) are derived at 95% confidence level. With ℓ±ℓ±=e±e±/μ±μ±/e±μ±, the observed lower limit on the mass of a doubly charged Higgs boson only coupling to left-handed leptons varies from 770 to 870 GeV (850 GeV expected) for B(H±±→ℓ±ℓ±)=100% and both the expected and observed mass limits are above 450 GeV for B(H±±→ℓ±ℓ±)=10% and any combination of partial branching ratios

Measurements of long-range azimuthal anisotropies and associated Fourier coefficients for pp collisions at √s=5.02 and 13 TeV and p+Pb collisions at √sNN=5.02 TeV with the ATLAS detector

ATLAS measurements of two-particle correlations are presented for √s=5.02 and 13 TeV ppcollisions and for √sNN=5.02 TeV p+Pb collisions at the LHC. The correlation functions are measured as a function of relative azimuthal angle Δϕ, and pseudorapidity separation Δη, using charged particles detected within the pseudorapidity interval |η|2, is studied using a template fitting procedure to remove a “back-to-back” contribution to the correlation function that primarily arises from hard-scattering processes. In addition to the elliptic, cos (2Δϕ), modulation observed in a previous measurement, the pp correlation functions exhibit significant cos (3Δϕ) and cos (4Δϕ) modulation. The Fourier coefficients vn, n associated with the cos (nΔϕ) modulation of the correlation functions for n=2–4 are measured as a function of charged-particle multiplicity and charged-particle transverse momentum. The Fourier coefficients are observed to be compatible with cos (nϕ) modulation of per-event single-particle azimuthal angle distributions. The single-particle Fourier coefficients vn are measured as a function of charged-particle multiplicity, and charged-particle transverse momentum for n=2–4. The integrated luminosities used in this analysis are, 64nb−1 for the √s=13 TeV pp data, 170 nb−1 for the √ s = 5.02 TeV pp data, and 28 nb−1 for the √sNN = 5.02 TeV p+Pb data

Searches for the Zγ decay mode of the Higgs boson and for new high-mass resonances in pp collisions at √s=13 TeV with the ATLAS detector

This article presents searches for the Zγ decay of the Higgs boson and for narrow high-mass resonances decaying to Zγ, exploiting Z boson decays to pairs of electrons or muons. The data analysis uses 36.1 fb−1 of pp collisions at √s=13 recorded by the ATLAS detector at the CERN Large Hadron Collider. The data are found to be consistent with the expected Standard Model background. The observed (expected — assuming Standard Model pp → H → Zγ production and decay) upper limit on the production cross section times the branching ratio for pp → H → Zγ is 6.6. (5.2) times the Standard Model prediction at the 95% confidence level for a Higgs boson mass of 125.09 GeV. In addition, upper limits are set on the production cross section times the branching ratio as a function of the mass of a narrow resonance between 250 GeV and 2.4 TeV, assuming spin-0 resonances produced via gluon-gluon fusion, and spin-2 resonances produced via gluon-gluon or quark-antiquark initial states. For high-mass spin-0 resonances, the observed (expected) limits vary between 88 fb (61 fb) and 2.8 fb (2.7 fb) for the mass range from 250 GeV to 2.4 TeV at the 95% confidence level