The nature of the human T cell response to the cancer antigen 5T4 is determined by the balance of regulatory and inflammatory T cells of the same antigen-specificity: implications for vaccine design

The oncofoetal antigen 5T4 is a promising T cell target in the context of colorectal cancer, as demonstrated by a recent clinical study where 5T4-specific T cell responses, induced by vaccination or cyclophosphamide, were associated with a significantly prolonged survival of patients with metastatic disease. Whilst Th1-type (IFN-γ+) responses specific to 5T4, and other oncofoetal antigens, are often readily detectable in early stage CRC patients and healthy donors, their activity is suppressed as the cancer progresses by CD4+CD25hiFoxp3+ regulatory T cells (Treg) which contribute to the immunosuppressive environment conducive to tumour growth. This study mapped the fine specificity of Th1 and Treg cell responses to the 5T4 protein. Surprisingly, both immunogenic peptides and those recognised by Tregs clustered in the same HLA-DR transcending epitope-rich hotspots within the 5T4 protein. Similarly, regions of low Th1-cell immunogenicity also did not contain peptides capable of stimulating Tregs, further supporting the notion that Treg and Th1 cells recognise the same peptides. Understanding the rules which govern the balance of Th1 and Treg cells responding to a given peptide specificity is, therefore, of fundamental importance to designing strategies for manipulating the balance in favour of Th1 cells, and thus the most effective anti-cancer T cell responses

The Iterative Mindset Method: a neuroscientific theoretical approach for sustainable behavior change and weight-loss in digital medicine

Abstract With the growing prevalence of chronic conditions driving 85% of all healthcare costs, digital health offers a promising opportunity to reverse disease and improve health at-scale. The healthcare industry’s predominant approach to behavior change is performance-based with a focus on goals and tracking. This has not reversed the epidemic of chronic diseases and also can harm chronically ill and vulnerable patients via perceived failure-induced loss of motivation. Still nascent, the digital health industry is uniquely positioned to adopt and scale new and better behavior change approaches. In this paper, we present the theoretical foundation and initial findings of a neuroscience-based behavior change approach—what we call the Iterative Mindset MethodTM. We discuss its promise, as a potentially more effective, neuroscience-based approach to changing health behaviors long-term, particularly in vulnerable populations. We conclude with avenues for future research

Création et évaluation d'un programme d'éducation du patient asthmatique (service de pneumologie-Hôpital de Longjumeau 91)

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Personal Growth and Wellbeing: An Iterative Mindset Assessment and Perspective

Interest in personal growth is expanding in both the popular press and the scientific literature. These expansions incorporate varied theoretical approaches and multiple areas of life. In the current work, we propose a novel perspective that focuses on managing failure to reach self-improvement goals and improving wellbeing. Specifically, we introduce an iterative mindset, which is the belief that making adaptations combined with deliberate practice and neutralizing of failure is critical for lasting transformations. We seek to contribute to the personal growth and mindset literature in two key ways. First, we developed and validated a new measure, called an Iterative Mindset Inventory (IMI), examining factor structure, reliability, and validity. Second, we investigated the links between iterative mindsets, self-improvement, and wellbeing, extending existing work on the power of beliefs to shape self-development. In both studies (Study 1, N = 871; Study 2, N = 345), we incorporated online samples that resembled the adult population of the United States. In Study 1, we found evidence for the proposed theoretical three-factor structure of an iterative mindset, which we label iterate, practice, and assess. In Study 2, using a longitudinal approach across three weeks, we confirmed the three-factor structure and found high test–retest reliability. Iterative mindsets were also positively linked to weight-loss success across both studies and to self-efficacy and wellbeing in Study 2

A long peptide from MELOE-1 contains multiple HLA class II T cell epitopes in addition to the HLA-A*0201 epitope: an attractive candidate for melanoma vaccination

International audienceCD4(+) T cells contribute importantly to the antitumor T cell response, and thus, long peptides comprising CD4 and CD8 epitopes may be efficient cancer vaccines. We have previously identified an overexpressed antigen in melanoma, MELOE-1, presenting a CD8(+) T cell epitope, MELOE-1(36-44), in the HLA-A*0201 context. A T cell repertoire against this epitope is present in HLA-A*0201+ healthy subjects and melanoma patients and the adjuvant injection of TIL containing MELOE-1 specific CD8(+) T cells to melanoma patients was shown to be beneficial. In this study, we looked for CD4(+) T cell epitopes in the vicinity of the HLA-A*0201 epitope. Stimulation of PBMC from healthy subjects with MELOE-1(26-46) revealed CD4 responses in multiple HLA contexts and by cloning responsive CD4(+) T cells, we identified one HLA-DRβ1*1101-restricted and one HLA-DQβ1*0603-restricted epitope. We showed that the two epitopes could be efficiently presented to CD4(+) T cells by MELOE-1-loaded dendritic cells but not by MELOE-1+ melanoma cell-lines. Finally, we showed that the long peptide MELOE-1(22-46), containing the two optimal class II epitopes and the HLA-A*0201 epitope, was efficiently processed by DC to stimulate CD4(+) and CD8(+) T cell responses in vitro, making it a potential candidate for melanoma vaccination

Abwasserbehandlung aus der Textilveredelung durch Kombination verschiedener Membranfilterverfahren und einer mikrobiellen Biozoenose auf einem Festbettreaktor zum Zwecke des Recycling Abschlussbericht

SIGLEAvailable from TIB Hannover: F01B1002 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDeutsche Bundesstiftung Umwelt, Osnabrueck (Germany)DEGerman