Pathological characterization of tumor immune microenvironment (Time) in malignant pleural mesothelioma

SIMPLE SUMMARY: Tumor immune microenvironment is an important structural component of malignant pleural mesothelioma that contributes to disease growth support and progression. Its study and pathological characterization are important tools to find new biomarkers for advanced therapeutic strategies. ABSTRACT: Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13–15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients’ genetic predisposition and tumor genomic profile. The chronic inflammatory response to asbestos fibers leads to a unique tumor immune microenvironment (TIME) composed of a heterogeneous mixture of stromal, endothelial, and immune cells, and relative composition and interaction among them is suggested to bear prognostic and therapeutic implications. TIME in MPM is known to be constituted by immunosuppressive cells, such as type 2 tumor-associated macrophages and T regulatory lymphocytes, plus the expression of several immunosuppressive factors, such as tumor-associated PD-L1. Several studies in recent years have contributed to achieve a greater understanding of the pathogenetic mechanisms in tumor development and pathobiology of TIME, that opens the way to new therapeutic strategies. The study of TIME is fundamental in identifying appropriate prognostic and predictive tissue biomarkers. In the present review, we summarize the current knowledge about the pathological characterization of TIME in MPM

A modified vimentin histological score helps recognize pulmonary sarcomatoid carcinoma in small biopsy samples

Background: As pulmonary sarcomatoid carcinomas (PSCs) are life-threatening tumors, an improvement in their recognition in small-sized tumor samples is clinically warranted. Materials and Methods: Preoperative biopsy samples and paired surgical specimens from 20 pleomorphic carcinomas, two pulmonary blastomas and one carcinosarcoma (training set) were studied for vimentin immunohistochemistry. A modified vimentin histologic score (M-VHS) was devised by multiplying three independently assessed parameters, i.e. the percentage of positive cells (from 0 to 5+, by quintiles), the intensity of immunostaining (low=1 vs. strong=2) and the distribution pattern within the cytoplasm (partial=1 vs. diffuse=2), so ranging from 0 to 20. Forty-eight consecutive and independent cases of non-small cell lung carcinoma (NSCLC), including two additional cases of PSC, were used as control groups (validation set). Results: No differences in M-VHS were found between biopsies and surgical specimens of PSC, thus confirming the occurrence of stable epithelial mesenchymal transition (EMT) and hence the specific diagnosis of PSC. All types of PSC shared the same M-VHS. The M-VHS of 46 conventional NSCLC was by far lower (p<0.0001), whereas two additional cases of PSC showed the same results as the training set. Poorly differentiated NSCLC with marked pleomorphism but not stable EMT did not exhibit significantly increased M-VHS values. Conclusion: M-VHS helped in morphological analysis to render more definite diagnoses on small biopsies of PSC

Longitudinal Emittance Blow-Up in the LHC

The LHC relies on Landau damping for longitudinal stability. To avoid decreasing the stability margin at high energy, the longitudinal emittance must be continuously increased during the acceleration ramp. Longitudinal blow-up provides the required emittance growth. The method was implemented through the summer of 2010. We inject band-limited RF phase-noise in the main accelerating cavities during the whole ramp of about 11 minutes. Synchrotron frequencies change along the energy ramp, but the digitally created noise tracks the frequency change. The position of the noise-band, relative to the nominal synchrotron frequency, and the bandwidth of the spectrum are set by pre-defined constants, making the diffusion stop at the edges of the demanded distribution. The noise amplitude is controlled by feedback using the measurement of the average bunch length. This algorithm reproducibly achieves the programmed bunch length of about 1.2 ns (4 ) at flat top with low bunch-to-bunch scatter and provides a stable beam for physics coast

Measurement and analysis of SPS kicker magnet heating and outgassing with Different Bunch Spacing

Fast kicker magnets are used to inject beam into and eject beam out of the CERN SPS accelerator ring. These kickers are generally ferrite loaded transmission line type magnets with a rectangular shaped aperture through which the beam passes. Unless special precautions are taken the impedance of the ferrite yoke can provoke significant beam induced heating, over several hours, even above the Curie temperature of the ferrite. At present the nominal bunch spacing in the SPS is 25 ns, however for an early stage of LHC operation it is preferable to have 50 ns bunch spacing. Machine Development (MD) studies have been carried out with an inter-bunch spacing of 25 ns, 50 ns or 75 ns. For some of the SPS kicker magnets the 75 ns bunch spacing resulted in considerable beam induced heating. In addition the MDs showed that 50 ns bunch spacing could result in a very rapid pressure rise in the kicker magnet and thus cause an interlock. This paper discusses the MD observations of the SPS kickers and analyses the available data to provide explanations for the phenomena: possible remedies are also discussed