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

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

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

Shell evolution approaching the N=20 island of inversion : Structure of 26Na

The levels in 26Na with single particle character have been observed for the first time using the d(25Na, pγ) reaction at 5 MeV/nucleon. The measured excitation energies and the deduced spectroscopic factors are in good overall agreement with (0+1)hω shell model calculations performed in a complete spsdfp basis and incorporating a reduction in the N=20 gap. Notably, the 1p3/2 neutron configuration was found to play an enhanced role in the structure of the low-lying negative parity states in 26Na, compared to the isotone 28Al. Thus, the lowering of the 1p3/2 orbital relative to the 0f7/2 occurring in the neighbouring Z=10 and 12 nuclei - 25,27Ne and 27,29Mg - is seen also to occur at Z=11 and further strengthens the constraints on the modelling of the transition into the island of inversion

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.

Single-particle structure of neutron-rich Sr isotopes via 2H(94,95,96Sr,p)^2H(^94,95,96Sr, p) reactions

Background: The region around neutron number N=60 in the neutron-rich Sr and Zr nuclei is one of the most dramatic examples of a ground-state shape transition from (near) spherical below N=60 to strongly deformed shapes in the heavier isotopes. Purpose: The single-particle structure of Sr95-97 approaching the ground-state shape transition at Sr98 has been investigated via single-neutron transfer reactions using the (d,p) reaction in inverse kinematics. These reactions selectively populate states with a large overlap of the projectile ground state coupled to a neutron in a single-particle orbital. Method: Radioactive Sr94,95,96 nuclei with energies of 5.5 AMeV were used to bombard a CD2, where D denotes H2, target. Recoiling light charged particles and γ rays were detected using a quasi-4π silicon strip detector array and a 12-element Ge array. The excitation energy of states populated was reconstructed employing the missing mass method combined with γ-ray tagging and differential cross sections for final states were extracted. Results: A reaction model analysis of the angular distributions allowed for firm spin assignments to be made for the low-lying 352, 556, and 681 keV excited states in Sr95 and a constraint has been placed on the spin of the higher-lying 1666 keV state. Angular distributions have been extracted for ten states populated in the H2(Sr95,p)Sr96 reaction, and constraints have been provided for the spins and parities of several final states. Additionally, the 0, 167, and 522 keV states in Sr97 were populated through the H2(Sr96,p) reaction. Spectroscopic factors for all three reactions were extracted. Conclusions: Results are compared to shell-model calculations in several model spaces and the structure of low-lying states in Sr94 and Sr95 is well described. The spectroscopic strength of the 0+ and 2+ states in Sr96 is significantly more fragmented than predicted. The spectroscopic factors for the H2(Sr96,p)Sr97 reaction suggest that the two lowest-lying excited states have significant overlap with the weakly deformed ground state of Sr96, but the ground state of Sr97 has a different structure

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