30 research outputs found
Cosmicflows-2: The Data
Cosmicflows-2 is a compilation of distances and peculiar velocities for over
8000 galaxies. Numerically the largest contributions come from the
luminosity-linewidth correlation for spirals, the TFR, and the related
Fundamental Plane relation for E/S0 systems, but over 1000 distances are
contributed by methods that provide more accurate individual distances:
Cepheid, Tip of the Red Giant Branch, Surface Brightness Fluctuation, SNIa, and
several miscellaneous but accurate procedures. Our collaboration is making
important contributions to two of these inputs: Tip of the Red Giant Branch and
TFR. A large body of new distance material is presented. In addition, an effort
is made to assure that all the contributions, our own and those from the
literature, are on the same scale. Overall, the distances are found to be
compatible with a Hubble Constant H_0 = 74.4 +-3.0 km/s/Mpc. The great interest
going forward with this data set will be with velocity field studies.
Cosmicflows-2 is characterized by a great density and high accuracy of distance
measures locally, falling to sparse and coarse sampling extending to z=0.1.Comment: To be published in Astronomical Journal. Two extensive tables to be
available on-line. Table 1 available at http://edd.ifa.hawaii.edu select
catalog `Cosmicflows-2 Distances
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