ALDH3A1 overexpression in melanoma and lung tumors drives cancer stem cell expansion, impairing immune surveillance through enhanced PD-L1 output

Melanoma and non-small-cell lung carcinoma (NSCLC) cell lines are characterized by an intrinsic population of cancer stem-like cells (CSC), and high expression of detoxifying isozymes, the aldehyde dehydrogenases (ALDHs), regulating the redox state. In this study, using melanoma and NSCLC cells, we demonstrate that ALDH3A1 isozyme overexpression and activity is closely associated with a highly aggressive mesenchymal and immunosuppressive profile. The contribution of ALDH3A1 to the stemness and immunogenic status of melanoma and NSCLC cells was evaluated by their ability to grow in 3D forming tumorspheres, and by the expression of markers for stemness, epithelial to mesenchymal transition (EMT), and inflammation. Furthermore, in specimens from melanoma and NSCLC patients, we investigated the expression of ALDH3A1, PD-L1, and cyclooxygenase-2 (COX-2) by immunohistochemistry. We show that cells engineered to overexpress the ALDH3A1 enzyme enriched the CSCs population in melanoma and NSCLC cultures, changing their transcriptome. In fact, we found increased expression of EMT markers, such as vimentin, fibronectin, and Zeb1, and of pro-inflammatory and immunosuppressive mediators, such as NFkB, prostaglandin E2, and interleukin-6 and-13. ALDH3A1 overexpression enhanced PD-L1 output in tumor cells and resulted in reduced proliferation of peripheral blood mononuclear cells when co-cultured with tumor cells. Furthermore, in tumor specimens from melanoma and NSCLC patients, ALDH3A1 expression was invariably correlated with PD-L1 and the pro-inflammatory marker COX-2. These findings link ALDH3A1 expression to tumor stemness, EMT and PD-L1 expression, and suggest that aldehyde detoxification is a redox metabolic pathway that tunes the immunological output of tumors

Amplitude analysis of the Λb0→pK−γ decay

The resonant structure of the radiative decay Λb0→pK−γ in the region of proton-kaon invariant-mass up to 2.5 GeV/c2 is studied using proton-proton collision data recorded at centre-of-mass energies of 7, 8, and 13 TeV collected with the LHCb detector, corresponding to a total integrated luminosity of 9 fb−1. Results are given in terms of fit and interference fractions between the different components contributing to this final state. Only Λ resonances decaying to pK− are found to be relevant, where the largest contributions stem from the Λ(1520), Λ(1600), Λ(1800), and Λ(1890) states

Enhanced production of Λb0\Lambda_{b}^{0} baryons in high-multiplicity pppp collisions at s=13\sqrt{s} = 13 TeV

The production rate of $\Lambda_{b}^{0}$ baryons relative to $B^{0}$ mesons in $pp$ collisions at a center-of-mass energy $\sqrt{s} = 13$ TeV is measured by the LHCb experiment. The ratio of $\Lambda_{b}^{0}$ to $B^{0}$ production cross-sections shows a significant dependence on both the transverse momentum and the measured charged-particle multiplicity. At low multiplicity, the ratio measured at LHCb is consistent with the value measured in $e^{+}e^{-}$ collisions, and increases by a factor of $\sim2$ with increasing multiplicity. At relatively low transverse momentum, the ratio of $\Lambda_{b}^{0}$ to $B^{0}$ cross-sections is higher than what is measured in $e^{+}e^{-}$ collisions, but converges with the $e^{+}e^{-}$ ratio as the momentum increases. These results imply that the evolution of heavy $b$ quarks into final-state hadrons is influenced by the density of the hadronic environment produced in the collision. Comparisons with a statistical hadronization model and implications for the mechanisms enforcing quark confinement are discussed.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-027.html (LHCb public pages

Studies of η\eta and η′\eta' production in pppp and ppPb collisions

The production of $\eta$ and $\eta'$ mesons is studied in proton-proton and proton-lead collisions collected with the LHCb detector. Proton-proton collisions are studied at center-of-mass energies of $5.02$ and $13~{\rm TeV}$, and proton-lead collisions are studied at a center-of-mass energy per nucleon of $8.16~{\rm TeV}$. The studies are performed in center-of-mass rapidity regions $2.5<y_{\rm c.m.}<3.5$ (forward rapidity) and $-4.0<y_{\rm c.m.}<-3.0$ (backward rapidity) defined relative to the proton beam direction. The $\eta$ and $\eta'$ production cross sections are measured differentially as a function of transverse momentum for $1.5<p_{\rm T}<10~{\rm GeV}$ and $3<p_{\rm T}<10~{\rm GeV}$, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for $\eta$ and $\eta'$ mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of $\eta$ mesons are also used to calculate $\eta/\pi^0$ cross section ratios, which show evidence of a deviation from the world average. These studies offer new constraints on mass-dependent nuclear effects in heavy-ion collisions, as well as $\eta$ and $\eta'$ meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb public pages

Fraction of χc\chi_c decays in prompt J/ψJ/\psi production measured in pPb collisions at sNN=8.16\sqrt{s_{NN}}=8.16 TeV

The fraction of $\chi_{c1}$ and $\chi_{c2}$ decays in the prompt $J/\psi$ yield, $F_{\chi c}=\sigma_{\chi_c \to J/\psi}/\sigma_{J/\psi}$, is measured by the LHCb detector in pPb collisions at $\sqrt{s_{NN}}=8.16$ TeV. The study covers the forward ($1.5<y^*<4.0$) and backward ($-5.0<y^*<-2.5$) rapidity regions, where $y^*$ is the $J/\psi$ rapidity in the nucleon-nucleon center-of-mass system. Forward and backward rapidity samples correspond to integrated luminosities of 13.6 $\pm$ 0.3 nb$^{-1}$ and 20.8 $\pm$ 0.5 nb$^{-1}$, respectively. The result is presented as a function of the $J/\psi$ transverse momentum $p_{T,J/\psi}$ in the range 1$<p_{T, J/\psi}<20$ GeV/$c$. The $F_{\chi c}$ fraction at forward rapidity is compatible with the LHCb measurement performed in $pp$ collisions at $\sqrt{s}=7$ TeV, whereas the result at backward rapidity is 2.4 $\sigma$ larger than in the forward region for $1<p_{T, J/\psi}<3$ GeV/$c$. The increase of $F_{\chi c}$ at low $p_{T, J/\psi}$ at backward rapidity is compatible with the suppression of the $\psi$(2S) contribution to the prompt $J/\psi$ yield. The lack of in-medium dissociation of $\chi_c$ states observed in this study sets an upper limit of 180 MeV on the free energy available in these pPb collisions to dissociate or inhibit charmonium state formation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-028.html (LHCb public pages

A measurement of ΔΓs\Delta \Gamma_{s}

Using a dataset corresponding to $9~\mathrm{fb}^{-1}$ of integrated luminosity collected with the LHCb detector between 2011 and 2018 in proton-proton collisions, the decay-time distributions of the decay modes $B_s^0 \rightarrow J/\psi \eta'$ and $B_s^0 \rightarrow J/\psi \pi^{+} \pi^{-}$ are studied. The decay-width difference between the light and heavy mass eigenstates of the $B_s^0$ meson is measured to be $\Delta \Gamma_s = 0.087 \pm 0.012 \pm 0.009 \, \mathrm{ps}^{-1}$, where the first uncertainty is statistical and the second systematic.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-025.htm

Search for CP\textit{CP} violation in the phase space of D0→KS0K±π∓D^{0} \rightarrow K_{S}^{0} K^{\pm} \pi^{\mp} decays with the energy test

A search for $\textit{CP}$ violation in $D^{0} \rightarrow K_{S}^{0} K^{+} \pi^{-}$ and $D^{0} \rightarrow K_{S}^{0} K^{-} \pi^{+}$ decays is reported. The search is performed using an unbinned model-independent method known as the energy test that probes local $\textit{CP}$ violation in the phase space of the decays. The data analysed correspond to an integrated luminosity of $5.4~$fb$^{-1}$ collected in proton-proton collisions by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=13$~TeV, amounting to approximately 950000 and 620000 signal candidates for the $D^{0} \rightarrow K_{S}^{0} K^{-} \pi^{+}$ and $D^{0} \rightarrow K_{S}^{0} K^{+} \pi^{-}$ modes, respectively. The method is validated using $D^{0} \rightarrow K^{-} \pi^{+} \pi^{-} \pi^{+}$ and $D^{0} \rightarrow K_{S}^{0} \pi^{+} \pi^{-}$ decays, where $\textit{CP}$-violating effects are expected to be negligible, and using background-enhanced regions of the signal decays. The results are consistent with $\textit{CP}$ symmetry in both the $D^{0} \rightarrow K_{S}^{0} K^{-} \pi^{+}$ and the $D^{0} \rightarrow K_{S}^{0} K^{+} \pi^{-}$ decays, with $p$-values for the hypothesis of no $\textit{CP}$ violation of 70% and 66%, respectively.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-019.html (LHCb public pages

Observation of strangeness enhancement with charmed mesons in high-multiplicity pPbp\mathrm{Pb} collisions at sNN=8.16 \sqrt {s_{\mathrm{NN}}}=8.16\,TeV

The production of prompt $D^+_{s}$ and $D^+$ mesons is measured by the LHCb experiment in proton-lead ($p\mathrm{Pb}$) collisions in both the forward ($1.5<y^*<4.0$) and backward ($-5.0<y^*<-2.5$) rapidity regions at a nucleon-nucleon center-of-mass energy of $\sqrt {s_{\mathrm{NN}}}=8.16\,$TeV. The nuclear modification factors of both $D^+_{s}$ and $D^+$ mesons are determined as a function of transverse momentum, $p_{\mathrm{T}}$, and rapidity. In addition, the $D^+_{s}$ to $D^+$ cross-section ratio is measured as a function of the charged particle multiplicity in the event. An enhanced $D^+_{s}$ to $D^+$ production in high-multiplicity events is observed for the whole measured $p_{\mathrm{T}}$ range, in particular at low $p_{\mathrm{T}}$ and backward rapidity, where the significance exceeds six standard deviations. This constitutes the first observation of strangeness enhancement in charm quark hadronization in high-multiplicity $p\mathrm{Pb}$ collisions. The results are also qualitatively consistent with the presence of quark coalescence as an additional charm quark hadronization mechanism in high-multiplicity proton-lead collisions.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-021.html (LHCb public pages