118 research outputs found
Towards a European Pillar of Social Rights: upgrading the EU social acquis. College of Europe Policy Brief #1.17, January 2017
Executive Summary
> The European Commission has recently
launched a ‘European Pillar of Social Rights’. The
Pillar consists of a broad range of social principles.
> The European Union’s social acquis, comprised
of the EU Charter of Fundamental Rights, Treaty
provisions, legislation and case law, already
provides a floor of social rights, protecting
workers’ health and safety, equal treatment and
job security.
> However, several lacunae in, and challenges to,
the EU social acquis currently exist, relating to its
scope of protection, its effective enforcement
and its possible conflict with other EU rights, such
as the Charter’s freedom to conduct a business.
> As a contribution to the consultation on the
Pillar initiative, we have reflected on how these
lacunae can be addressed and the EU social
acquis strengthened to enhance the ability to live
up to citizens’ expectations that the Union indeed
aims at the ‘well-being of its people’ (Art.3(1)
TEU).
> This policy brief contributes to the much-needed
broad reflection on ‘social Europe’ through a
focused and realistic fourfold proposal for
adopting (1) a Directive for the Protection of
Dependent Workers, ensuring the application of
the existing EU social and labour law measures to
all dependent workers (2) a Protection against
Precarious Work Directive, (3) a Directive for the
Enforcement of Workers Rights and (4) a
Declaration safeguarding the integrity of the
social acquis as an EU floor for worker protection
Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome)
Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9
The INTERPHONE study: design, epidemiological methods, and description of the study population
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
The Essence of the Fundamental Right to Equal Treatment: Back to the Origins
status: publishe
An Ever-Changing Union? Perspectives on the Future of EU Law in Honour of Allan Rosas
status: Published onlin
Institutionalising Solidarity: A Genuine Challenge for Europe
Dialogue with Silvana Sciarra on Solidarity and Conflict. European Social Law in Crisis, Cambridge: Cambridge University Press, 2018status: publishe
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