Role of Antigen Spread and Distinctive Characteristics of Immunotherapy in Cancer Treatment

Contains fulltext : 174163.pdf (publisher's version ) (Open Access)Immunotherapy is an important breakthrough in cancer. US Food and Drug Administration-approved immunotherapies for cancer treatment (including, but not limited to, sipuleucel-T, ipilimumab, nivolumab, pembrolizumab, and atezolizumab) substantially improve overall survival across multiple malignancies. One mechanism of action of these treatments is to induce an immune response against antigen-bearing tumor cells; the resultant cell death releases secondary (nontargeted) tumor antigens. Secondary antigens prime subsequent immune responses (antigen spread). Immunotherapy-induced antigen spread has been shown in clinical studies. For example, in metastatic castration-resistant prostate cancer patients, sipuleucel-T induced early immune responses to the immunizing antigen (PA2024) and/or the target antigen (prostatic acid phosphatase). Thereafter, most patients developed increased antibody responses to numerous secondary proteins, several of which are expressed in prostate cancer with functional relevance in cancer. The ipilimumab-induced antibody profile in melanoma patients shows that antigen spread also occurs with immune checkpoint blockade. In contrast to chemotherapy, immunotherapy often does not result in short-term changes in conventional disease progression end points (eg, progression-free survival, tumor size), which may be explained, in part, by the time taken for antigen spread to occur. Thus, immune-related response criteria need to be identified to better monitor the effectiveness of immunotherapy. As immunotherapy antitumor effects take time to evolve, immunotherapy in patients with less advanced cancer may have greater clinical benefit vs those with more advanced disease. This concept is supported by prostate cancer clinical studies with sipuleucel-T, PSA-TRICOM, and ipilimumab. We discuss antigen spread with cancer immunotherapy and its implications for clinical outcomes

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Abundance analysis, spectral variability, and search for the presence of a magnetic field in the typical PGa star HD 19400

The aim of this study is to carry out an abundance determination, to search for spectral variability and for the presence of a weak magnetic field in the typical PGa star HD 19400. High-resolution, high signal-to-noise High Accuracy Radial-velocity Planet Searcher (HARPS) spectropolarimetric observations of HD 19400 were obtained at three different epochs in 2011 and 2013. For the first time, we present abundances of various elements determined using an ATLAS12 model, including the abundances of a number of elements not analysed by previous studies, such as Ne I, Ga II, and Xe II. Several lines of As II are also present in the spectra of HD 19400. To study the variability, we compared the behaviour of the line profiles of various elements. We report on the first detection of anomalous shapes of line profiles belonging to Mn and Hg, and the variability of the line profiles belonging to the elements Hg, P, Mn, Fe, and Ga. We suggest that the variability of the line profiles of these elements is caused by their non-uniform surface distribution, similar to the presence of chemical spots detected in HgMn stars. The search for the presence of a magnetic field was carried out using the moment technique and the Singular Value Decomposition (SVD) method. Our measurements of the magnetic field with the moment technique using 22 Mn II lines indicate the potential existence of a weak variable longitudinal magnetic field on the first epoch. The SVD method applied to the Mn II lines indicates &lt;Bz&gt; = -76 &plusmn; 25 G on the first epoch, and at the same epoch the SVD analysis of the observations using the Fe II lines shows &lt;Bz&gt; = -91 &plusmn; 35 G. The calculated false alarm probability values, 0.008 and 0.003, respectively, are above the value 10-3, indicating no detection.</p

Late Quaternary inundation and desiccation of Megalake Chad traced in dust records from the Equatorial Atlantic Ocean

Modern Lake Chad has shrunk in area by around 90 % since the 1960s under the twin pressures of climate change and increasing water demand. During the early to mid Holocene, the Chad basin featured a megalake with an area approximately 100 times larger than its modern remnant. In the mid/late Holocene (approximately 5000 years ago), this megalake dried out leaving behind vast deposits of readily deflated fine-grained sediments that are suggested to contribute ∼25 % of the annual total global atmospheric mineral dust load. Erosion has obliterated much of the evidence of earlier North African humid periods within the Lake Chad basin, limiting our understanding of the relationship between global/regional climatology, local hydrology and dust export. Here, we present new records of thorium-normalized flux estimates of mineral dust and its radiogenic isotope composition deposited at Ocean Drilling Program Site 662, situated downwind of Megalake Chad underneath the North African winter dust plume, in the equatorial Atlantic Ocean. Our records show that sediments of the Megalake Chad basin have a distinct neodymium isotopic signature that can be traced thousands of kilometers downwind from their source when the megalake basin was dry and dust-active, whereas the fingerprint of its input was strongly suppressed at times of high lake levels. Our results show that marine sedimentary archives can preserve uninterrupted proxy records of climate-driven hydrological change on the continents, in this case, a bellwether region of Africa that features the world's most active dust source, the Bodélé Depression

WEAVE First Light observations: Origin and Dynamics of the Shock Front in Stephan’s Quintet

© 2024 The Author(s). Published by Oxford University Press on behalf of Royal Astronomical Society. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/We present a detailed study of the large-scale shock front in Stephan’s Quintet, a by-product of past and ongoing interactions. Using integral-field spectroscopy from the new William Herschel Telescope Enhanced Area Velocity Explorer (WEAVE), recent 144 MHz observations from the LOFAR Two-metre Sky Survey, and archi v al data from the Very Large Array and JWST , we obtain new measurements of key shock properties and determine its impact on the system. Harnessing the WEAVE large integral f ield unit’s field of view (90 × 78 arcsec 2 ), spectral resolution ( R ∼ 2500), and continuous wavelength coverage across the optical band, we perform robust emission-line modelling and dynamically locate the shock within the multiphase intergalactic medium with higher precision than previously possible. The shocking of the cold gas phase is hypersonic, and comparisons with shock models show that it can readily account for the observed emission-line ratios. In contrast, we demonstrate that the shock is relatively weak in the hot plasma visible in X-rays (with Mach number of M ∼ 2 –4), making it inefficient at producing the relativistic particles needed to explain the observed synchrotron emission. Instead, we propose that it has led to an adiabatic compression of the medium, which has increased the radio luminosity 10-fold. Comparison of the Balmer line-derived extinction map with the molecular gas and hot dust observed with JWST suggests that pre-existing dust may have survived the collision, allowing the condensation of H 2 –a key channel for dissipating the shock energy.Peer reviewe

The Voyage of Metals in the Universe from Cosmological to Planetary Scales: the need for a Very High-Resolution, High Throughput Soft X-ray Spectrometer

Metals form an essential part of the Universe at all scales. Without metals we would not exist, and the Cosmos would look completely different. Metals are primarily born through nuclear processes in stars. They leave their cradles through winds or explosions, and then start their journey through space. This can lead them in and out of astronomical objects on all scales, ranging from comets, planets, stars, entire galaxies, groups and clusters of galaxies to the largest structures of the Universe. Their wanderings are fundamental in determining how these objects, and the entire universe, evolve. In addition, their bare presence can be used to trace what these structures look like. The scope of this paper is to highlight the most important open astrophysical problems that will be central in the next decades and for which a deep understanding of the Universe-wandering metals, their physical and kinematical states and their chemical composition represents the only viable solution. The majority of these studies can only be efficiently performed through High Resolution Spectroscopy in the soft X-ray band.Large scale structure and cosmolog

Production of pizero and eta mesons at large transverse momenta in pp and pBe interactions at 530 and 800 GeV/c

We present results on the production of high transverse momentum pizero and eta mesons in pp and pBe interactions at 530 and 800 GeV/c. The data span the kinematic ranges: 1 < p_T < 10 GeV/c in transverse momentum and 1.5 units in rapidity. The inclusive pizero cross sections are compared with next-to-leading order QCD calculations and to expectations based on a phenomenological parton-k_T model.Comment: RevTeX, 63 pages, 25 figures, to be submitted to Phys. Rev.