The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC

Measurement of angular and CP asymmetries in D0→π+π-μ+μ- and D0→K+K-μ+μ- decays

The first measurements of the forward-backward asymmetry of the dimuon pair (A_{FB}), the triple-product asymmetry (A_{2ϕ}), and the charge-parity-conjugation asymmetry (A_{CP}), in D0→π+π-μ+μ- and D0→K+K-μ+μ- decays are reported. They are performed using data from proton-proton collisions collected with the LHCb experiment from 2011 to 2016, corresponding to a total integrated luminosity of 5  fb^{-1}. The asymmetries are measured to be A_{FB}(D^{0}→π^{+}π^{-}μ^{+}μ^{-})=(3.3±3.7±0.6)%, A_{2ϕ}(D^{0}→π^{+}π^{-}μ^{+}μ^{-})=(-0.6±3.7±0.6)%, A_{CP}(D^{0}→π^{+}π^{-}μ^{+}μ^{-})=(4.9±3.8±0.7)%, A_{FB}(D^{0}→K^{+}K^{-}μ^{+}μ^{-})=(0±11±2)%, A_{2ϕ}(D^{0}→K^{+}K^{-}μ^{+}μ^{-})=(9±11±1)%, A_{CP}(D^{0}→K^{+}K^{-}μ^{+}μ^{-})=(0±11±2)%, where the first uncertainty is statistical and the second systematic. The asymmetries are also measured as a function of the dimuon invariant mass. The results are consistent with the standard model predictions

Highlights from the LHCb experiment

We report recent results by the LHCb collaboration in heavy-ion collisions in collider and fixed-target mode at the LHC. A large variety of measurements show the potential of LHCb in nuclear collisions

Search for beautiful tetraquarks in the <i>ϒ</i>(1<i>S</i>)μ⁺μ⁻ invariant-mass spectrum

International audienceThe ϒ(1S)μ$^{+}$μ$^{−}$ invariant-mass distribution is investigated for a possible exotic meson state composed of two b quarks and two $\overline{b}$ quarks, ${X}_{b\overline{b}b\overline{b}}$ . The analysis is based on a data sample of pp collisions recorded with the LHCb detector at centre-of-mass energies $\sqrt{s}=7$ , 8 and 13 TeV, corresponding to an integrated luminosity of 6.3 fb$^{−1}$. No significant excess is found, and upper limits are set on the product of the production cross-section and the branching fraction as functions of the mass of the ${X}_{b\overline{b}b\overline{b}}$ state. The limits are set in the fiducial volume where all muons have pseudorapidity in the range [2.0, 5.0], and the ${X}_{b\overline{b}b\overline{b}}$ state has rapidity in the range [2.0, 4.5] and transverse momentum less than 15 GeV/c

Direct photon production at LHCb

At small Bjorken-x, the large gluon number density in the nucleon leads to gluon recombination competing with gluon splitting, which could result in saturation of the gluon PDF. This gluon saturation has yet to be conclusively observed. Direct photon production provides sensitivity to gluon densities in protons and nuclei, and the forward acceptance of LHCb detector allows for measurements of this process at low Bjorken-x, providing an ideal probe of saturation effects. Progress towards the measurement of forward direct photon production using the LHCb detector is presented

Measurement of the CKM angle γ using<i> B</i>^± → <i>DK</i>^± with D → K _S ⁰ π⁺π⁻, K _S ⁰ K⁺K⁻ decays

A binned Dalitz plot analysis of $B^\pm \to D K^\pm$ decays, with $D\to K_\text{S}^0\pi^+\pi^-$ and $D\to K_\text{S}^0K^+K^-$, is used to perform a measurement of the CP-violating observables $x_{\pm}$ and $y_{\pm}$, which are sensitive to the Cabibbo-Kobayashi-Maskawa angle $\gamma$. The analysis is performed without assuming any $D$ decay model, through the use of information on the strong-phase variation over the Dalitz plot from the CLEO collaboration. Using a sample of proton-proton collision data collected with the LHCb experiment in 2015 and 2016, and corresponding to an integrated luminosity of 2.0$\,\text{fb}^{-1}$, the values of the CP violation parameters are found to be $x_- = ( 9.0 \pm 1.7 \pm 0.7 \pm 0.4) \times 10^{-2}$, $y_- = ( 2.1 \pm 2.2 \pm 0.5 \pm 1.1) \times 10^{-2}$, $x_+ = (- 7.7 \pm 1.9 \pm 0.7 \pm 0.4) \times 10^{-2}$, and $y_+ = (- 1.0 \pm 1.9 \pm 0.4 \pm 0.9) \times 10^{-2}$. The first uncertainty is statistical, the second is systematic, and the third is due to the uncertainty on the strong-phase measurements. These values are used to obtain \gamma = \left(87\,^{+11}_{-12}\right)^\circ, $r_B = 0.086^{+ 0.013}_{-0.014}$, and $\delta_B = (101 \pm 11)^\circ$, where $r_B$ is the ratio between the suppressed and favoured $B$-decay amplitudes and $\delta_B$ is the corresponding strong-interaction phase difference. This measurement is combined with the result obtained using 2011 and 2012 data collected with the \lhcb experiment, to give \gamma = \left(80\,^{+10}_{\,-9}\right)^\circ, $r_B = 0.080 \pm 0.011$, and $\delta_B = (110 \pm 10)^\circ$.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2018-017.html. Version 2 includes minor changes made during journal revie

Evidence for an ηc(1S) π− Resonance in B0 → ηc(1S) K+ π− Decays

A Dalitz plot analysis of B0 → ηc(1S) K+ π− decays is performed using data samples of pp collisions collected with the LHCb detector at centre-of-mass energies of √s =7, 8 and 13 TeV, corresponding to a total integrated luminosity of 4.7 fb^−1. A satisfactory description of the data is obtained when including a contribution representing an exotic ηc(1S) π− resonant state. The significance of this exotic resonance is more than three standard deviations, while its mass and width are 4096 ± 20{−22}{+18} MeV and 152 ± 58{−35}{+60} MeV, respectively. The spin-parity assignments JP = 0+ and JP = 1− are both consistent with the data. In addition, the first measurement of the B0 → ηc(1S) K+ π− branching fraction is performed and gives B(B0 → ηc(1S) K+ π−) = (5.73 ± 0.24 ± 0.13 ± 0.66) × 10^−4, where the first uncertainty is statistical, the second systematic, and the third is due to limited knowledge of external branching fractions

Evidence for an ηc(1S)π- resonance in B0→ηc(1S)K+π- decays

A Dalitz plot analysis of B0→ηc(1S)K+π- decays is performed using data samples of pp collisions collected with the LHCb detector at centre-of-mass energies of s=7,8 and 13TeV , corresponding to a total integrated luminosity of 4.7fb-1 . A satisfactory description of the data is obtained when including a contribution representing an exotic ηc(1S)π- resonant state. The significance of this exotic resonance is more than three standard deviations, while its mass and width are 4096±20-22+18MeV and 152±58-35+60MeV , respectively. The spin-parity assignments JP=0+ and JP=1- are both consistent with the data. In addition, the first measurement of the B0→ηc(1S)K+π- branching fraction is performed and gives B(B0→ηc(1S)K+π-)=(5.73±0.24±0.13±0.66)×10-4, where the first uncertainty is statistical, the second systematic, and the third is due to limited knowledge of external branching fractions

Measurement of the time-integrated <i>CP</i> asymmetry in <i>D</i>⁰ → <i>K _S</i> ⁰ <i>K _S</i>⁰ decays

A measurement of the time-integrated $CP$ asymmetry in $D^0\rightarrow K^0_S K^0_S$ decays is reported. The data correspond to an integrated luminosity of about $2$ fb$^{-1}$ collected in 2015-2016 by the LHCb collaboration in $pp$ collisions at a centre-of-mass energy of $13$ TeV. The $D^0$ candidate is required to originate from a $D^{\ast +} \rightarrow D^0 \pi^+$ decay, allowing the determination of the flavour of the $D^0$ meson using the pion charge. The $D^0 \rightarrow K^{+}K^{-}$ decay, which has a well measured $CP$ asymmetry, is used as a calibration channel. The $CP$ asymmetry for $D^0\rightarrow K^0_S K^0_S$ is measured to be \begin{equation*} \mathcal{A}^{CP}(D^0\rightarrow K^0_S K^0_S) = (4.3\pm 3.4\pm 1.0)\%, \end{equation*} where the first uncertainty is statistical and the second is systematic. This result is combined with the previous LHCb measurement at lower centre-of-mass energies to obtain \begin{equation*} \mathcal{A}^{CP}(D^0\rightarrow K^0_S K^0_S) = (2.3\pm 2.8\pm 0.9)\%. \end{equation*}Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2018-012.htm