A5063056885- Cancer Immunotherapy and Biomarkers
- Bladder and Urothelial Cancer Treatments
- RNA and protein synthesis mechanisms
- Radiomics and Machine Learning in Medical Imaging
- Ferroptosis and cancer prognosis
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Urinary and Genital Oncology Studies
- Immunotherapy and Immune Responses
- Colorectal Cancer Treatments and Studies
- Adipose Tissue and Metabolism
- RNA modifications and cancer
- Sirtuins and Resveratrol in Medicine
- Cellular Mechanics and Interactions
- Genetic factors in colorectal cancer
- Caveolin-1 and cellular processes
- Cell Adhesion Molecules Research
- Lymphoma Diagnosis and Treatment
- Mycobacterium research and diagnosis
- Immune Response and Inflammation
- Endoplasmic Reticulum Stress and Disease
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Hypoxia, and Metabolism
- Polyamine Metabolism and Applications
Hôpital Laveran
2022
University of Leicester
2013-2022
Laboratoire Adhésion et inflammation
2019
Medical Research Council
2015-2018
University of Cambridge
2018
MRC Toxicology Unit
2014-2018
Aix-Marseille Université
2017-2018
Délégation Provence et Corse
2017
Inserm
2017
Centre National de la Recherche Scientifique
2017
Anti-PD-1 and PD-L1 antibodies (mAbs) are approved immunotherapy agents to treat metastatic non-small cell lung cancer (NSCLC) patients. Only a minority of patients responds these treatments biomarkers predicting response currently lacking.Immunoscore-Immune-Checkpoint (Immunoscore-IC), an in vitro diagnostic test, was used on 471 routine single FFPE-slides, the duplex-immunohistochemistry CD8 staining quantified using digital-pathology. Analytical validation performed two independent...
Abstract Human mRNA DeXD/H-box helicases are ubiquitous molecular motors that required for the majority of cellular processes involve RNA metabolism. One most abundant is eIF4A, which during initiation phase protein synthesis to unwind regions highly structured would otherwise impede scanning ribosome. Dysregulation associated with tumorigenesis, but little known about detailed relationships between helicase function and malignant phenotype in solid malignancies. Therefore,...
Abstract Biomarkers guiding the neoadjuvant use of immune-checkpoint blockers (ICB) are needed for patients with localized muscle-invasive bladder cancers (MIBC). Profiling tumor and blood samples, we found that follicular helper CD4+ T cells (TFH) among best therapeutic targets pembrolizumab correlating progression-free survival. TFH were associated tumoral CD8 PD-L1 expression at baseline induction tertiary lymphoid structures after pembrolizumab. Blood central memory accumulated in tumors...
Cooling and hypothermia are profoundly neuroprotective, mediated, at least in part, by the cold shock protein, RBM3. However, neuroprotective effector proteins induced RBM3 mechanisms which mRNAs encoding escape cooling-induced translational repression unknown. Here, we show that cooling induces reprogramming of translatome, including upregulation a new RTN3, reticulon protein implicated synapse formation. We report this has two mechanistic components. Thus, RTN3 both evades elongation is...
Significance Optimal antigenic stimulation through T-cell receptors is required by T lymphocytes to exert full expansion, effector functions, and memory cell differentiation. Suboptimal TCR influences both transcription of genes synthesis subsets proteins in a nonconcordant manner. Detailed polysome profiling revealed that weakly activated cells prioritized mRNA translation so specific transcripts were translationally sequestered. Strikingly, ribosome biogenesis was compromised at...
Abstract Mycolactone is the exotoxin virulence factor of Mycobacterium ulcerans that causes neglected tropical disease Buruli ulcer. We recently showed it to be a broad spectrum inhibitor Sec61-dependent co-translational translocation proteins into endoplasmic reticulum (ER). An outstanding question molecular pathway linking this its known cytotoxicity. have now used translational profiling better understand reprogramming occurs in cells exposed mycolactone. Gene ontology identified...
Background New and fully validated tests need to be brought into clinical practice improve the estimation of recurrence risk in patients with colon cancer. The aim this study was assess analytical performances Immunoscore (IS) show its contribution prognosis prediction. Methods Immunohistochemical staining CD3+ CD8+ T cells on adjacent sections cancer tissues were quantified core tumor invasive margin dedicated IS modules integrated digital pathology software. Staining intensity across...
Dysregulated expression of factors that control protein synthesis is associated with poor prognosis many cancers, but the underlying mechanisms are not well defined. Analysis diffuse large B-cell lymphoma (DLBCL) translatome revealed selective upregulation mRNAs encoding anti-apoptotic and DNA repair proteins. We show enhanced these proteins in DLBCL mediated by relief repression normally imposed structure 5'-untranslated regions their corresponding mRNAs. This process driven signaling...
408 Background: DPAI models have recently demonstrated the potential to improve risk stratification beyond routine clinical and pathologic variables. However, it is not known whether integrating information will enhance prognostic accuracy of validated gene expression tests. In this study, performance novel algorithms were assessed in context genomic classifier (GC). Methods: A prospectively collected cohort 9,874 patients with localized prostate cancer was retrieved from Veracyte GRID...
335 Background: Recent advances in AI have brought innovation to digital pathology problems with H&E whole slide images (WSI). Though some (DPAI) models been developed for survival analysis TCGA data, there is a lack of understanding as how DPAI predict progression free (PFS) the prostate dataset (PRAD). Nor comprehensive comparison versus genomic or clinical models. Batch effects were also ignored prior works. Methods: PRAD contains 392 patients WSI and data. batch effect was first...
Significance Oxidative stress is a critical contributor to aging-associated diseases, including neurodegeneration, cancer, and cardiovascular disease. Here, we demonstrate that the p53 family transcription factor TAp73 contributes oxidative response by participating in control of protein synthesis. Regulation mRNA translation ensures prompt efficient method overcome stress, depletion results aberrant ribosomal biogenesis impaired In particular, important for maintaining active mitochondrial...
Abstract We have used polysome profiling coupled to microarray analysis examine the translatome of a panel peripheral blood (PB) B cells isolated from 34 chronic lymphocytic leukaemia (CLL) patients. identified ‘ribosome-related’ signature in CLL patients with mRNAs encoding for ribosomal proteins and factors that modify RNA, e.g. DKC1 (which encodes dyskerin, pseudouridine synthase), showing reduced polysomal association decreased expression corresponding proteins. Our data suggest general...
Translational regulation plays a central role in the global gene expression of cell, and detection such has allowed deciphering critical biological mechanisms. Genome-wide studies translation (translatome) performed on microarrays represent substantial proportion studies, alongside with recent advances deep-sequencing methods. However, there been lack development specific processing methodologies that deal distinct nature translatome array data. In this study, we confirm polysome profiling...
Review on eIF4B, with data DNA/RNA, the protein encoded and where gene is implicated.
2509 Background: Anti-PD1 and PD-L1 antibodies (mAb) are immune checkpoint inhibitors (ICIs) to treat patients with metastatic non–small cell lung cancer (NSCLC). Unfortunately, only a handful of respond ICIs. Methods: A cohort NSCLC (n=133) treated anti-PD1 or anti-PD-L1 mAb in two independent care centers was evaluated. An 132 from another hospital used as validation. Immunoscore IC, an vitro diagnostic test (CE-IVD), on routine single FFPE slide, duplex immunohistochemistry CD8 staining...
Abstract The recruitment of leukocytes from blood vessels to inflamed zones is guided by biochemical and mechanical stimuli, with mechanisms only partially deciphered. We studied here the guidance flow primary human effector T lymphocytes crawling on substrates coated ligands integrins LFA-1 (α L β 2 ) VLA-4 4 1 ), showed that cells segregated in two populations opposite orientation for combined adhesion. Sharp decisions were shown rely a bistable mechanism between LFA-1-mediated upstream...
Abstract Artificial Intelligence (AI) along with Machine Learning (ML) techniques has long promised to accelerate Digital Pathology (DP) based cancer diagnosis. Despite the consensus regarding value of AI, lack visibility how ML algorithms work, prevents their wider adoption for human in vitro diagnostic (IVD) a highly regulated environment. A common ground becomes necessary order fully benefit from capabilities. HalioDx Immunoscore® was first immune scoring test validated IVD use leveraging...