Wide-field direct CCD observations supporting the Astro-1 Space Shuttle mission's Ultraviolet Imaging Telescope

Wide field direct CCD observations are being obtained to support and complement the vacuum-ultraviolet (VUV) images provided by Astro's Ultraviolet Imaging Telescope (UIT) during a Space Shuttle flight in December 1990. Because of the wide variety of projects addressed by UIT, the fields observed include (1) galactic supernova remnants such as the Cygnus Loop and globular clusters such as Omega Cen and M79; (2) the Magellanic Clouds, M33, M81, and other galaxies in the Local Group; and (3) rich clusters of galaxies, principally the Perseus cluster and Abell 1367. Ground-based observations have been obtained for virtually all of the Astro-1 UIT fields. The optical images allow identification of individual UV sources in each field and provide the long baseline in wavelength necessary for accurate analysis of UV-bright sources. To facilitate use of our optical images for analysis of UIT data and other projects, we plan to archive them, with the UIT images, at the National Space Science Data Center (NSSDC), where they will be universally accessible via anonymous FTP. The UIT, one of three telescopes comprising the Astro spacecraft, is a 38-cm f/9 Ritchey-Chretien telescope on which high quantum efficiency, solar-blind image tubes are used to record VUV images on photographic film. Five filters with passbands centered between 1250A and 2500A provide both VUV colors and a measurement of extinction via the 2200A dust feature. The resulting calibrated VUV pictures are 40 arcminutes in diameter at 2.5 arcseconds resolution. The capabilities of UIT, therefore, complement HST's WFPC: the latter has 40 times greater collecting area, while UIT's usable field has 170 times WFPC's field area

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival