The good and the bad of T cell cross-reactivity: challenges and opportunities for novel therapeutics in autoimmunity and cancer

T cells are main actors of the immune system with an essential role in protection against pathogens and cancer. The molecular key event involved in this absolutely central task is the interaction of membrane-bound specific T cell receptors with peptide-MHC complexes which initiates T cell priming, activation and recall, and thus controls a range of downstream functions. While textbooks teach us that the repertoire of mature T cells is highly diverse, it is clear that this diversity cannot possibly cover all potential foreign peptides that might be encountered during life. TCR cross-reactivity, i.e. the ability of a single TCR to recognise different peptides, offers the best solution to this biological challenge. Reports have shown that indeed, TCR cross-reactivity is surprisingly high. Hence, the T cell dilemma is the following: be as specific as possible to target foreign danger and spare self, while being able to react to a large spectrum of body-threatening situations. This has major consequences for both autoimmune diseases and cancer, and significant implications for the development of T cell-based therapies. In this review, we will present essential experimental evidence of T cell cross-reactivity, implications for two opposite immune conditions, i.e. autoimmunity vs cancer, and how this can be differently exploited for immunotherapy approaches. Finally, we will discuss the tools available for predicting cross-reactivity and how improvements in this field might boost translational approaches

Adhérence fibre d'acier - matrice cimentaire dans les mortiers fibrés à hautes températures

https://www.polytech.univ-savoie.fr/fileadmin/polytech_autres_sites/sites/augc2012/actes/Contribution1192.pdfNational audienceRÉSUMÉ. Dans cette étude, nous nous sommes intéressés au comportement mécanique des mortiers renforcés de fibres d'acier. Tout d'abord, nous étudions la résistance à la flexion de ces mortiers après traitement thermique. Ensuite, nous nous intéressons à l'évolution de l'adhérence fibre - matrice en fonction de la température. Ces deux études indiquent une dégradation des caractéristiques physico-mécaniques dès 500°C. Des observations au MEB mettent en évidence une corrosion à haute température des fibres d'aciers. Cette corrosion débute à 500°C. A 800°C, près de 85% de la section des fibres est corrodée ce qui explique les pertes de caractéristiques mécaniques observées précédemment. ABSTRACT. In this study, we investigate the mechanical behaviour of steel fibres reinforced mortars. First, we study the flexural strength of mortars after heat treatment. Next, we investigate the evolution of the fibre - matrix adhesion function of temperature. Both studies indicate a deterioration of physical-mechanical characteristics at 500 °C. SEM observations show a high temperature corrosion of steel fibres. The corrosion starts at 500 ° C. At 800 °C, nearly 85% of the fibres section is corroded which explains the loss of the mechanical properties

A pilot study exploring quality of life experienced by patients undergoing negative pressure wound therapy as part of their wound care treatment compared to patients receiving standard wound care

The use of Negative Pressure Wound Therapy (NPWT) has been widely documented as a technique to help heal complex wounds. This paper presents the findings of a preliminary study which aimed to explore quality of life experienced by patients undergoing negative pressure wound therapy (NPWT) as part of their wound care treatment in comparison to that of patients with a wound using traditional (standard) wound care therapies. A quasi-experimental study was undertaken, with patients treated in wound care/vascular clinics with chronic/acute wounds. Quality of life impact was measured using the Cardiff Wound Impact Schedule and administered post consent at timed intervals. Our results identified that there were no real differences in quality of life scores recorded by patients over the 12 week period. Although there was no overall interaction between the therapies used for wound healing, NPWT did have an effect on social life: during the first 2 weeks of the application of therapy, patients in the NPWT group reported an increase in the social life domain. The authors conclude that true QoL can only be elicited if an accurate baseline is established or if data is collected over a long enough period to allow comparison of scores over time

Toward harmonized phenotyping of human myeloid-derived suppressor cells by flow cytometry: results from an interim study

There is an increasing interest for monitoring circulating myeloid-derived suppressor cells (MDSCs) in cancer patients, but there are also divergences in their phenotypic definition. To overcome this obstacle, the Cancer Immunoguiding Program under the umbrella of the Association of Cancer Immunotherapy is coordinating a proficiency panel program that aims at harmonizing MDSC phenotyping. After a consultation period, a two-stage approach was designed to harmonize MDSC phenotype. In the first step, an international consortium of 23 laboratories immunophenotyped 10 putative MDSC subsets on pretested, peripheral blood mononuclear cells of healthy donors to assess the level of concordance and define robust marker combinations for the identification of circulating MDSCs. At this stage, no mandatory requirements to standardize reagents or protocols were introduced. Data analysis revealed a small intra-laboratory, but very high inter-laboratory variance for all MDSC subsets, especially for the granulocytic subsets. In particular, the use of a dead-cell marker altered significantly the reported percentage of granulocytic MDSCs, confirming that these cells are especially sensitive to cryopreservation and/or thawing. Importantly, the gating strategy was heterogeneous and associated with high inter-center variance. Overall, our results document the high variability in MDSC phenotyping in the multicenter setting if no harmonization/standardization measures are applied. Although the observed variability depended on a number of identified parameters, the main parameter associated with variation was the gating strategy. Based on these findings, we propose further efforts to harmonize marker combinations and gating parameters to identify strategies for a robust enumeration of MDSC subsets

Transferable Integrated Optical SU8 Devices: From Micronic Waveguides to 1D-Nanostructures

International audienceWe report on optical components for integrated optics applications at the micro-and nanoscale. Versatile shapes and dimensions are achievable due to the liquid phase processability of SU8 resist. On the one hand, by adjusting the UV-lithography process, waveguiding structures are patterned and released from their original substrate. They can be replaced on any other substrate and also immerged in liquid wherein they still show off efficient light confinement. On the other hand, filled and hollow 1D-nanostructures are achievable by the wetting template method. By exploiting the large range of available SU8 viscosities, nanowires of diameter ranging between 50 nm and 240 nm, as well as nanotubes of controllable wall thickness are presented. Optical injection, propagation, and coupling in such nanostructures are relevant for highly integrated devices

Targeted therapy in renal cell carcinoma: moving from molecular agents to specific immunotherapy

Non-specific immunotherapy has been for a long time a standard treatment option for patients with metastatic renal cell carcinoma but was redeemed by specific targeted molecular therapies, namely the VEGF and mTOR inhibitors. After moving treatment for mRCC to specific molecular agents with a well-defined mode of action, immunotherapy still needs this further development to increase its accuracy. Nowadays, an evolution from a rather non-specific cytokine treatment to sophisticated targeted approaches in specific immunotherapy led to a re-launch of immunotherapy in clinical studies. Recent steps in the development of immunotherapy strategies are discussed in this review with a special focus on peptide vaccination which aims at a tumor targeting by specific T lymphocytes. In addition, different combinatory strategies with immunomodulating agents like cyclophosphamide or sunitinib are outlined, and the effects of immune checkpoint modulators as anti-CTLA-4 or PD-1 antibodies are discussed

Electrical and magnetic properties of La0.67Ba0.33Mn1−x (Me) x O3 perovskite manganites: case of manganese substituted by trivalent (Me = Cr) and tetravalent (Me = Ti) elements

International audienceThe effects of non-magnetic Ti4+ substitution on the structural, electrical and magnetic properties of La0.67Ba0.33Mn1−x Ti x O3 (0≤x≤0.1) are investigated and compared to those existing in La0.67Ba0.33Mn1−x Cr x O3 (magnetic Cr3+). The structural refinement by the Rietveld method revealed that Ti-doped samples crystallize in the cubic lattice with space group Pm3¯m , while samples with Cr crystallize in the hexagonal setting of the rhombohedral R3¯C space group for identical contents of dopant. The most relevant structural features are an increase of the lattice parameters, of the cell volume and of the inter-ionic distances with increasing Ti doping level. Both series of samples show a decrease of the paramagnetic-ferromagnetic transition temperature when the amount of chromium or titanium increases. Transport measurements show that when increasing the metal doping, the resistivity increases whereas the metallic behavior of the parent compound La0.67Ba0.33MnO3 is destroyed. For a substitution higher than 5 at.% of Ti and 10 at.% of Cr, the samples exhibit a semiconducting behavior in the whole range of temperature, for which the electronic transport can be explained by variable range hopping and/or small polaron hopping models

Lipofection with Synthetic mRNA as a Simple Method for T-Cell Immunomonitoring.

The quantification of T-cell immune responses is crucial for the monitoring of natural and treatment-induced immunity, as well as for the validation of new immunotherapeutic approaches. The present study presents a simple method based on lipofection of synthetic mRNA in mononuclear cells as a method to determine in vitro T-cell responses. We compared several commercially available transfection reagents for their potential to transfect mRNA into human peripheral blood mononuclear cells and murine splenocytes. We also investigated the impact of RNA modifications in improving this method. Our results demonstrate that antigen-specific T-cell immunomonitoring can be easily and quickly performed by simple lipofection of antigen-coding mRNA in complex immune cell populations. Thus, our work discloses a convenient solution for the in vitro monitoring of natural or therapy-induced T-cell immune responses

Sr1-xBaxSnO3 system applied in the photocatalytic discoloration of an azo-dye

International audienceSemiconductor materials have received substantial attention as photocatalysts for controlling water pollution. Among these materials, perovskite-structured SrSnO3 is a promising candidate for this application, whereas BaSnO3 exhibits very low activity. In the present work, Sr1−xBaxSnO3 (x = 0, 0.25, 0.50, 0.75 and 1) was synthesized by solid-state reaction and was applied in the photocatalytic discoloration of the organic dye Remazol Golden Yellow. The perovskite structure was obtained for all compositions of the solid solutions with both Sr2+ and Ba2+ present in the lattice. A remarkable change in the short-range symmetry was observed as the amount of Ba2+ increased, and this change led to a decrease in the band gap of the material. Although the BaSnO3 was not active toward water photolysis, the discoloration induced by this perovskite was twice that induced by SrSnO3. The two materials appear to feature different mechanisms of photodegradation: the direct mechanism prevails in the case of BaSnO3, whereas the indirect mechanism appears to play a key role in the case of SrSnO3