Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment

Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don’t respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development. Experimental cancer immunology and therap

Ethical challenges in nursing homes - staff's opinions and experiences with systematic ethics meetings with participation of residents' relatives.

Background Many ethical problems exist in nursing homes. These include, for example, decision-making in end-of-life care, use of restraints and a lack of resources. Aims The aim of the present study was to investigate nursing home staffs’ opinions and experiences with ethical challenges and to find out which types of ethical challenges and dilemmas occur and are being discussed in nursing homes. Methods The study used a two-tiered approach, using a questionnaire on ethical challenges and systematic ethics work, given to all employees of a Norwegian nursing home including nonmedical personnel, and a registration of systematic ethics discussions from an Austrian model of good clinical practice. Results Ninety-one per cent of the nursing home staff described ethical problems as a burden. Ninety per cent experienced ethical problems in their daily work. The top three ethical challenges reported by the nursing home staff were as follows: lack of resources (79%), end-of-life issues (39%) and coercion (33%). To improve systematic ethics work, most employees suggested ethics education (86%) and time for ethics discussion (82%). Of 33 documented ethics meetings from Austria during a 1-year period, 29 were prospective resident ethics meetings where decisions for a resident had to be made. Agreement about a solution was reached in all 29 cases, and this consensus was put into practice in all cases. Residents did not participate in the meetings, while relatives participated in a majority of case discussions. In many cases, the main topic was end-of-life care and life-prolonging treatment. Conclusions Lack of resources, end-of-life issues and coercion were ethical challenges most often reported by nursing home staff. The staff would appreciate systematic ethics work to aid decision-making. Resident ethics meetings can help to reach consensus in decision-making for nursing home patients. In the future, residents’ participation should be encouraged whenever possible

CONTRIBUTION A LA MISE EN PLACE D'UN SYSTEME D'INFORMATION GEOGRAPHIQUE POUR L'ANALYSE DU RISQUE "PESTE BOVINE" EN CENTRAFRIQUE

La République de Centre Afrique est située prés de l'un des derniers creusets infectieux de peste bovine en Afrique. Entre l'arrêt du programme PARC et le début du programme PACE la gestion du risque de réintroduction et de diffusion de la peste bovine devait faire l'objet d'une attention soutenue. Un Système d'Information Géographique (SIG) constitue un outil efficace pour la gestion de ce risque. La mise en place d'un tel système nécessitait la récolte et le traitement de nombreuses informations suivant une démarche logique. L'environnement géographique et administratif du pays a été reproduit, les données épidémiologiques ont été saisies et les inventaires des moyens humains et matériels ont été commencés. La réunion et l'informatisation de l'ensemble de ces données ont pris du temps et se sont heurtés à certaines contraintes inhérentes à la Centrafrique. Bien que je n'aie pas eu le temps de finir la mise en place du SIG, celui-ci était déjà fonctionnel pour un certain nombre de tâches. Son achèvement devrait en faire un outil efficace pour analyser les risques de réintroduction et de diffusion de la peste bovine, pour gérer le Plan d'Intervention d'Urgence en cas d'épidémie et pour exploiter les résultats des différentes activités de lutte et de surveillance déjà en place en Centrafrique et qui sont amenées à se développer avec le programme PACE.MAISONS-ALFORT-Ecole Vétérin (940462302) / SudocSudocFranceF