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

Examination of direct-photon and pion production in proton-nucleon collisions

We present a study of inclusive direct-photon and pion production in hadronic interactions, focusing on a comparison of the ratio of gamma/pi0 yields with expectations from next-to-leading order perturbative QCD (NLO pQCD). We also examine the impact of a phenomenological model involving k_T smearing (which approximates effects of additional soft-gluon emission) on absolute predictions for photon and pion production and their ratio.Comment: 20 pages, 12 figures. Minor changes in wording and in figure

The next-to-leading order forward jet vertex in the small-cone approximation

We consider within QCD collinear factorization the process p+p to jet + jet +X, where two forward high-$p_T$ jets are produced with a large separation in rapidity $\Delta y$ (Mueller-Navelet jets). In this case the (calculable) hard part of the reaction receives large higher-order corrections $\sim \alpha^n_s (\Delta y)^n$, which can be accounted for in the BFKL approach. In particular, we calculate in the next-to-leading order the impact factor (vertex) for the production of a forward high-$p_T$ jet, in the approximation of small aperture of the jet cone in the pseudorapidity-azimuthal angle plane. The final expression for the vertex turns out to be simple and easy to implement in numerical calculations.Comment: 32 pages, 4 figures; a few comments and one reference added; a few inessential misprints removed; version to appear on JHE

D^* production from e^+e^- to ep collisions in NLO QCD

Fragmentation functions for D mesons, based on the convolution of a perturbative part, related to the heavy quark perturbative showering, and a non-perturbative model for its hadronization into the meson, are used to describe D^* production in e^+e^- and ep collisions. The non-perturbative part is determined by fitting the e^+e^- data taken by ARGUS and OPAL at 10.6 and 91.2 GeV respectively. When fitting with a non perturbative Peterson fragmentation function and using next-to-leading evolution for the perturbative part, we find an epsilon parameter sensibly different from the one commonly used, which is instead found with a leading order fit. The use of this new value is shown to increase considerably the cross section for D^* production at HERA, suggesting a possible reconciliation between the next-to-leading order theoretical predictions and the experimental data.Comment: 20 pages, LaTeX2e, 8 Postscript figure

Metadata schema to support FAIR data in scanning electron microscopy

The development and the adoption of metadata schemas and standards are a key aspect in data management. In this paper, we introduce our approach to a metadata model in the field of Materials Science. We present the specific use case of a metadata schema for Scanning Electron Microscopy, a characterization technique which is routinely used in Materials Science. This metadata schema is aiming to be a de-facto standard which will be openly available for reuse and further extension to other electron microscopy techniques

kt Effects in Direct-Photon Production

We discuss the phenomenology of initial-state parton-kt broadening in direct-photon production and related processes in hadron collisions. After a brief summary of the theoretical basis for a Gaussian-smearing approach, we present a systematic study of recent results on fixed-target and collider direct-photon production, using complementary data on diphoton and pion production to provide empirical guidance on the required amount of kt broadening. This approach provides a consistent description of the observed pattern of deviation of next-to-leading order QCD calculations relative to the direct-photon data, and accounts for the shape and normalization difference between fixed-order perturbative calculations and the data. We also discuss the uncertainties in this phenomenological approach, the implications of these results on the extraction of the gluon distribution of the nucleon, and the comparison of our findings to recent related work.Comment: LaTeX, uses revtex and epsf, 37 pages, 15 figure

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1- Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy

PURPOSE. To investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME).CASES AND METHODS. Ninety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intraarterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel number. We also correlated these TME factors with the presence of histological high-risk factors (HHRF+) and RB anaplasia grade (AG).RESULTS. After CHT, a decrease in both RB burden and Ki67 positivity was observed. In parallel, most subsets of TI-ICs, PD-1+ TI-ICs, gliosis, and PD-L1 protein expression significantly increased (P < 0.001, P = 0.02, P < 0.001, respectively). Vessel number did not significantly vary. Age, HHRFs+ and AG were significantly different between primary and chemoreduced RBs (P < 0.001, P = 0.006, P = 0.001, respectively) and were correlated with most TME factors.CONCLUSIONS. CHT modulates host antitumor immunity by reorienting the RB TME from anergic into an active, CD8+, PD-L1+ hot state. Furthermore, some clinicopathological characteristics of RB correlate with several factors of TME. Our study adds data in favor of the possibility of a new therapeutic scenario in human RB