Neutrophil and Natural Killer Cell Interactions in Cancers: Dangerous Liaisons Instructing Immunosuppression and Angiogenesis

The tumor immune microenvironment (TIME) has largely been reported to cooperate on tumor onset and progression, as a consequence of the phenotype/functional plasticity and adaptation capabilities of tumor-infiltrating and tumor-associated immune cells. Immune cells within the tumor micro (tissue-local) and macro (peripheral blood) environment closely interact by cell-to-cell contact and/or via soluble factors, also generating a tumor-permissive soil. These dangerous liaisons have been investigated for pillars of tumor immunology, such as tumor associated macrophages and T cell subsets. Here, we reviewed and discussed the contribution of selected innate immunity effector cells, namely neutrophils and natural killer cells, as \u201csoloists\u201d or by their \u201cdangerous liaisons\u201d, in favoring tumor progression by dissecting the cellular and molecular mechanisms involved

Human Dental Pulp Mesenchymal Stem Cell-Derived Soluble Factors Combined with a Nanostructured Scaffold Support theGeneratio of a Vascular Network In Vivo

Among all strategies directed at developing new tools to support re-vascularization of damaged tissues, the use of pro-angiogenic soluble factors, derived from mesenchymal stem cells (MSCs), appears a promising approach for regenerative medicine. Here, we compared the feasibility of two devices, generated by coupling soluble factors of human dental pulp mesenchymal stem cells (DPSCs), with a nanostructured scaffold, to support angiogenesis once transplanted in mice. DPSCs were obtained from impacted wisdom tooth removal, usually considered surgical waste material. After 28 days, we verified the presence of active blood vessels inside the scaffold through optical and scansion electron microscopy. The mRNA expression of surface antigens related to macrophage polarization (CD68, CD80, CD86, CD163, CD206), as well as pro-angiogenic markers (CD31, CD34, CD105, Angpt1, Angpt2, CDH5) was evaluated by real-time PCR. Our results demonstrate the capability of DPSC–scaffold and DPSC soluble factors–scaffold to support angiogenesis, similarly to adipose stem cells, whereas the absence of blood vessels was found in the scaffold grafted alone. Our results provide evidence that DPSC-conditioned medium can be proposed as a cell-free preparation able to support angiogenesis, thus, providing a relevant tool to overcome the issues and restrictions associated with the use of cells

The GALEX Arecibo SDSS survey: III. Evidence for the Inside-Out Formation of Galactic Disks

We analyze a sample of galaxies with stellar masses greater than $10^{10} M_{\odot}$ and with redshifts in the range $0.025<z<0.05$ for which HI mass measurements are available from the GALEX Arecibo SDSS Survey (GASS) or from the Arecibo Legacy Fast ALFA survey (ALFALFA). At a given value of $M_*$, our sample consists primarily of galaxies that are more HI-rich than average. We constructed a series of three control samples for comparison with these HI-rich galaxies. As expected, HI-rich galaxies differ strongly from galaxies of same stellar mass that are selected without regard to HI content. The majority of these differences are attributable to the fact that galaxies with more gas are bluer and more actively star-forming. In order to identify those galaxy properties that are causally connected with HI content, we compare results derived for the HI sample with those derived for galaxies matched in stellar mass, size and NUV-$r$ colour. The only photometric property that is clearly attributable to increasing HI content, is the colour gradient of the galaxy. Galaxies with larger HI fractions have bluer, more actively star-forming outer disks compared to the inner part of the galaxy. HI-rich galaxies also have larger $g$-band radii compared to $i$-band radii. Our results are consistent with the "inside-out" picture of disk galaxy formation, which has commonly served as a basis for semi-analytic models of the formation of disks in the context of Cold Dark Matter cosmologies. The lack of any intrinsic connection between HI fraction and galaxy asymmetry suggests that gas is accreted smoothly onto the outer disk.Comment: 18 pages, 20 figures. Accepted for publication in MNRAS. GASS publications and released data can be found at http://www.mpa-garching.mpg.de/GASS/index.ph

Natural killer cells as key players of tumor progression and angiogenesis: old and novel tools to divert their pro-tumor activities into potent anti-tumor effects

Immune cells, as a consequence of their plasticity, can acquire altered phenotype/functions within the tumor microenvironment (TME). Some of these aberrant functions include attenuation of targeting and killing of tumor cells, tolerogenic/immunosuppressive behavior and acquisition of pro-angiogenic activities. Natural killer (NK) cells are effector lymphocytes involved in tumor immunosurveillance. In solid malignancies, tumor-associated NK cells (TANK cells) in peripheral blood and tumor-infiltrating NK (TINK) cells show altered phenotypes and are characterized by either anergy or reduced cytotoxicity. Here, we aim at discussing how NK cells can support tumor progression and how induction of angiogenesis, due to TME stimuli, can be a relevant part on the NK cell-associated tumor supporting activities. We will review and discuss the contribution of the TME in shaping NK cell response favoring cancer progression. We will focus on TME-derived set of factors such as TGF-\u3b2, soluble HLA-G, prostaglandin E2, adenosine, extracellular vesicles, and miRNAs, which can exhibit a dual function. On one hand, these factors can suppress NK cell-mediated activities but, on the other hand, they can induce a pro-angiogenic polarization in NK cells. Also, we will analyze the impact on cancer progression of the interaction of NK cells with several TME-associated cells, including macrophages, neutrophils, mast cells, cancer-associated fibroblasts, and endothelial cells. Then, we will discuss the most relevant therapeutic approaches aimed at potentiating/restoring NK cell activities against tumors. Finally, supported by the literature revision and our new findings on NK cell pro-angiogenic activities, we uphold NK cells to a key host cellular paradigm in controlling tumor progression and angiogenesis; thus, we should bear in mind NK cells like a TME-associated target for anti-tumor therapeutic approaches

MAGNUM survey: A MUSE-Chandra resolved view on ionized outflows and photoionization in the Seyfert galaxy NGC 1365

Context. Ionized outflows, revealed by broad asymmetric wings of the [O III] lambda 5007 line, are commonly observed in active galactic nuclei (AGN) but the low intrinsic spatial resolution of the observations has generally prevented a detailed characterization of their properties. The MAGNUM survey aims at overcoming these limitations by focusing on the nearest AGN, including NGC 1365, a nearby Seyfert galaxy (D similar to 17 Mpc), hosting a low-luminosity active nucleus (L-bol similar to 2 x 10(43) erg s(-1)). Aims. We want to obtain a detailed picture of the ionized gas in the central similar to 5 kpc of NGC 1365 in terms of physical properties, kinematics, and ionization mechanisms. We also aim to characterize the warm ionized outflow as a function of distance from the nucleus and its relation with the nuclear X-ray wind. Methods. We employed optical integral-field spectroscopic observations from VLT/MUSE to investigate the warm ionized gas and Chandra ACIS-S X-ray data for the hot highly-ionized phase. We obtained flux, kinematic, and diagnostic maps of the optical emission lines, which we used to disentangle outflows from gravitational motions in the disk and measure the gas properties down to a spatial resolution of similar to 70 pc. We then performed imaging spectroscopy on Chandra ACIS-S data guided by the matching with MUSE maps. Results. The [O III] emission mostly traces a kpc-scale biconical outflow ionized by the AGN having velocities up to similar to 200 km s(-1). H alpha emission traces instead star formation in a circumnuclear ring and along the bar, where we detect non-circular streaming gas motions. Soft X-rays are predominantly due to thermal emission from the star-forming regions, but we manage to isolate the AGN photoionized component which nicely matches the [O III] emission. The mass outflow rate of the extended ionized outflow is similar to that of the nuclear X-ray wind and then decreases with radius, implying that the outflow either slows down or that the AGN activity has recently increased. However, the hard X-ray emission from the circumnuclear ring suggests that star formation might in principle contribute to the outflow. The integrated mass outflow rate, kinetic energy rate, and outflow velocity are broadly consistent with the typical relations observed in more luminous AGN

Tocilizumab for treatment of severe covid-19 patients: Preliminary results from smatteo covid19 registry (smacore)

Objective: This study aimed to assess the role of Tocilizumab therapy (TCZ) in terms of ICU admission and mortality rate of critically ill patients with severe COVID-19 pneumonia. Design: Patients with COVID-19 pneumonia were prospectively enrolled in SMAtteo COvid19 REgistry (SMACORE). A retrospective analysis of patients treated with TCZ matched using propensity score to patients treated with Standard Of Care (SOC) was conducted. Setting: The study was conducted at IRCCS Policlinico San Matteo Hospital, Pavia, Italy, from March 14, 2020 to March 27, 2020. Participants: Patients with a confirmed diagnosis of COVID-19 hospitalized in our institution at the time of TCZ availability. Interventions: TCZ was administered to 21 patients. The first administration was 8 mg/kg (up to a maximum 800 mg per dose) of Tocilizumab intravenously, repeated after 12 h if no side effects were reported after the first dose. Main Outcomes and Measures: ICU admission and 7-day mortality rate. Secondary outcomes included clinical and laboratory data. Results: There were 112 patients evaluated (82 were male and 30 were female, with a median age of 63.55 years). Using propensity scores, the 21 patients who received TCZ were matched to 21 patients who received SOC (a combination of hydroxychloroquine, azithromycin and prophylactic dose of low weight heparin). No adverse event was detected following TCZ administration. This study found that treatment with TCZ did not significantly affect ICU admission (OR 0.11; 95% CI between 0.00 and 3.38; p = 0.22) or 7-day mortality rate (OR 0.78; 95% CI between 0.06 and 9.34; p = 0.84) when compared with SOC. Analysis of laboratory measures showed significant interactions between time and treatment regarding C-Reactive Protein (CRP), alanine aminotransferase (ALT), platelets and international normalized ratio (INR) levels. Variation in lymphocytes count was observed over time, irrespective of treatment. Conclusions: TCZ administration did not reduce ICU admission or mortality rate in a cohort of 21 patients. Additional data are needed to understand the effect(s) of TCZ in treating patients diagnosed with COVID-19