13 research outputs found
Federated Identity Management for Research Collaborations
This white-paper expresses common requirements of Research Communities seeking to leverage Identity Federation for
Authentication and Authorisation. Recommendations are made to Stakeholders to guide the future evolution of Federated
Identity Management in a direction that better satisfies research use cases. The authors represent research communities,
Research Services, Infrastructures, Identity Federations and Interfederations, with a joint motivation to ease collaboration
for distributed researchers. The content has been edited collaboratively by the Federated Identity Management for
Research (FIM4R) Community, with input sought at conferences and meetings in Europe, Asia and North America
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
Using Singularity for Geant4-based simulations on HPC infrastructures
Containers represent a well-known paradigm, which
has been widely adopted in enterprises thanks to its ability to
conveniently address issues related to fast delivery, portability
and life-cycle management of software. On the contrary, they
received so far modest attention in the scientific community and
their adoption in experimental physics computing has progressed
relatively slowly. Scientific applications are typically complex
because of several factors. Among them the heterogeneous system
requirements, i.e. specific versions of libraries and compilers, and
the frequent updates, normally developed by researchers who
are not familiar with software engineering principles. Containers
would greatly foster scientific activities in terms of software
availability, reproducibility, and shareability, in particular for
small research groups that need to couple scientific, sysadmin and
programming skills in one or a few persons. In this contribution
we briefly present an experience using Singularity containers
for running a multithreaded simulation based on Geant4 using
different INFN computing infrastructures
Comparison of Geant4 electromagnetic physics models against the NIST reference data
The Geant4 Simulation Toolkit provides an ample set of physics models describing electromagnetic interactions of particles with matter. This paper presents the results of a series of comparisons for the evaluation of Geant4 electromagnetic processes with respect to United States National Institute of Standards and Technologies (NIST) reference data. A statistical analysis was performed to estimate quantitatively the compatibility of Geant4 electromagnetic models with NIST data; the statistical analysis also highlighted the respective strengths of the different Geant4 models