Vaccination of stage III/IV melanoma patients with long NY-ESO-1 peptide and CpG-B elicits robust CD8(+) and CD4(+) T-cell responses with multiple specificities including a novel DR7-restricted epitope.

Long synthetic peptides and CpG-containing oligodeoxynucleotides are promising components for cancer vaccines. In this phase I trial, 19 patients received a mean of 8 (range 1-12) monthly vaccines s.c. composed of the long synthetic NY-ESO-179-108 peptide and CpG-B (PF-3512676), emulsified in Montanide ISA-51. In 18/18 evaluable patients, vaccination induced antigen-specific CD8(+) and CD4(+) T-cell and antibody responses, starting early after initiation of immunotherapy and lasting at least one year. The T-cells responded antigen-specifically, with strong secretion of IFNγ and TNFα, irrespective of patients' HLAs. The most immunogenic regions of the vaccine peptide were NY-ESO-189-102 for CD8(+) and NY-ESO-183-99 for CD4(+) T-cells. We discovered a novel and highly immunogenic epitope (HLA-DR7/NY-ESO-187-99); 7/7 HLA-DR7(+) patients generated strong CD4(+) T-cell responses, as detected directly ex vivo with fluorescent multimers. Thus, vaccination with the long synthetic NY-ESO-179-108 peptide combined with the strong immune adjuvant CpG-B induced integrated, robust and functional CD8(+) and CD4(+) T-cell responses in melanoma patients, supporting the further development of this immunotherapeutic approach

SturTOP project:Vulnerability and adaptability of the last population of the European Sturgeon (Acipenser sturio) to the environmental stress factors: Temperature, Oxygen, Polluants.

SturTOP is a multidisciplinary project launched in 2013 to investigate effects of chemical, thermal or hypoxic stress conditions on the health, the physiology, the behaviour and the adaptability of the first life stages of the European sturgeon. Experiments will be performed to evaluate responses of embryos and larvae exposed: i) in controlled conditions to environmental ranges of temperatures, oxygen and pollutant mixture, ii) to sediments collected from spawning grounds, iii) in situ. Studied effects will concern the individual fitness i.e. survival, ontogeny and behaviour as well as DNA damage, epigenetic modifications, gene expression and protein expression profiles. The same effects will be studied for 3 month-old farmed sturgeon (age of stocking) exposed in experimental systems which mimic the environmental conditions. In the wild, environmental exposure to pollutants will be evaluated thanks to individual dosimeters and to chemical analysis of stomach content. In a final step, a model will be built to simulate the future for a cohort subjected to multiple stresses. Expected results will give insights into the ability of this species to grow and to reproduce in the Gironde estuary and to adapt to changing environmental conditions. It could help decision-making by managers in charge of restoration plans

nmMLCK : a key player in intermittent hypoxia-induced inflammatory vascular remodeling ?

International audienc

nmMLCK : a key player in intermittent hypoxia-induced inflammatory vascular remodeling ?

International audienc

nmMLCK a key player in intermittent hypoxia-induced inflammatory vascular remodeling ?

International audienc

nmMLCK a key player in intermittent hypoxia-induced inflammatory vascular remodeling ?

International audienc

A glyphosate-based herbicide induces sub-lethal effects in early life stages and liver cell line of rainbow trout, Oncorhynchus mykiss

International audienc

Comparative developmental toxicity of conventional oils and diluted bitumen on early life stages of the rainbow trout (Oncorhynchus mykiss)

International audiencePetroleum hydrocarbons are widely used and transported, increasing the risks of spills to the environment. Although conventional oils are the most commonly produced, the production of unconventional oils (i.e. diluted bitumen or dilbit) is increasing. In this study, we compared the effects of conventional oils (Arabian Light and Lloydminster) and dilbits (Bluesky and Clearwater) on early life stages of a salmonid. To this end, aqueous fractions (WAF: water accommodated fraction) of these oils were extracted using mountain spring water. Rainbow trout (Oncorhynchus mykiss) larvae were exposed to 10 and 50% dilutions of these WAFs from hatching (340 DD; degree days) until yolk sac resorption (541 DD). Exposure to WAFs increased skeletal malformations (both dilbits) and hemorrhage (both conventional oils and Bluesky) and decreased head growth (Arabian Light). In addition, increases in EROD activity and DNA damage were measured for all oils and an increase in cyp1a gene expression was measured for Arabian Light, Bluesky and Clearwater. The PAH and C10single bondC50 concentrations were positively correlated to total larval EROD activity, whereas concentrations of total hydrocarbons, VOCs, PAHs, and C10single bondC50 were positively correlated to cyp1a expression. Total hydrocarbon, VOC, and C10single bondC50 concentrations were also negatively correlated to larval growth. This study supports that petroleum hydrocarbons are toxic to early developmental stages of rainbow trout and show that their degree and spectrum of toxicity depends on their chemical composition