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Your search keyword '"Axel Boukredine"' showing total 2 results
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2 results on '"Axel Boukredine"'

1. Decoding of the surfaceome and endocytome in primary glioblastoma cells identifies potential target antigens in the hypoxic tumor niche

Author

Kelin Gonçalves de Oliveira, Anna Bång-Rudenstam, Sarah Beyer, Axel Boukredine, Hugo Talbot, Valeria Governa, Maria C. Johansson, Ann-Sofie Månsson, Karin Forsberg-Nilsson, Johan Bengzon, Johan Malmström, Charlotte Welinder, and Mattias Belting

Subjects
Immunotherapy, Glioblastoma, Tumor antigens, Proteomics, Hypoxia, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Immunotherapies with antibody–drug-conjugates (ADC) and CAR-T cells, targeted at tumor surface antigens (surfaceome), currently revolutionize clinical oncology. However, target identification warrants a better understanding of the surfaceome and how it is modulated by the tumor microenvironment. Here, we decode the surfaceome and endocytome and its remodeling by hypoxic stress in glioblastoma (GBM), the most common and aggressive brain tumor in adults. We employed a comprehensive approach for global and dynamic profiling of the surfaceome and endocytosed (endocytome) proteins and their regulation by hypoxia in patient-derived GBM cultures. We found a heterogeneous surface-endocytome profile and a divergent response to hypoxia across GBM cultures. We provide a quantitative ranking of more than 600 surface resident and endocytosed proteins, and their regulation by hypoxia, serving as a resource to the cancer research community. As proof-of-concept, the established target antigen CD44 was identified as a commonly and abundantly expressed surface protein with high endocytic activity. Among hypoxia induced proteins, we reveal CXADR, CD47, CD81, BSG, and FXYD6 as potential targets of the stressed GBM niche. We could validate these findings by immunofluorescence analyses in patient tumors and by increased expression in the hypoxic core of GBM spheroids. Selected candidates were finally confronted by treatment studies, showing their high capacity for internalization and ADC delivery. Importantly, we highlight the limited correlation between transcriptomics and proteomics, emphasizing the critical role of membrane protein enrichment strategies and quantitative mass spectrometry. Our findings provide a comprehensive understanding of the surface-endocytome and its remodeling by hypoxia in GBM as a resource for exploration of targets for immunotherapeutic approaches in GBM.

Published
2024
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2. Radiotherapy induces specific miRNA expression profiles in glioblastoma exosomes

Author

Stéphanie Durand, Marie-Odile Jauberteau, Elise Deluche, Amel Rehailia, Sofiane Saada, Axel Boukredine, Pierre Clavère, Fabrice Lalloué, Alexandre Nivet, and Barbara Bessette

Subjects
education.field_of_study, Tumor microenvironment, Cell, Population, Context (language use), Biology, Microvesicles, medicine.anatomical_structure, Radioresistance, microRNA, medicine, Cancer research, Liquid biopsy, education
Abstract

BackgroundGlioblastoma (GBM) is the most aggressive and frequent primary brain tumor during adulthood. One of the major treatments is the association of surgery and a combination of chemo and radiotherapies. Despite its immediate efficiency, it fails to prevent the cancer recurrence in the irradiated area due to radioresistance mechanisms.MicroRNAs (miRNAs or miR) are small non-coding, single strand RNA molecules encoding to various specific genes and able to regulate their expression and induce the tumor cell survival leading to radioresistance. Small extracellular vesicles (EVs), or exosomes released by tumor cells in tumor microenvironment and blood circulation are able to transport and diffuse miRNAs and affect the microenvironment by spreading the miRNAs, which drive radioresistance.AimsTo identify the variations of miRNAs expression induced by irradiation in human glioblastoma U87-MG cells and their secreted exosomes collected in supernatants.To analyze the miRNAs variations in EVs-derived from the plasma of patients during radiotherapy, in order to identify a miRNA signature induced by radiotherapy in a liquid biopsy.Materiel and methodsU87-MG cells were cultured on plates and exposed to irradiation. miRNAs analyzes were performed in cells and in EVs isolated from cell supernatants to determine miRNAs expressions both in cells and in secreted exosomes before and after irradiation.Plasma-derived EVs were collected from 4 glioblastoma patients before and after surgery and radiotherapy treatments.ConclusionThe analysis of miRNAs expression profiles in both GBM cells and their derived EVs revealed that miR profile changes after irradiation. However, the number of similar miR between cells or EVs, following cell irradiation, was restricted to 3 miRs alone suggesting that the irradiation-induced changes in the miR profile in the cells and their EVs are not closely linked. In this context, the miR profile in EVs from patients plasma was investigated to establish a potential link with the miRNAs profile observed in EVs from irradiated cells and to assess its relationship with the response to radiotherapy. Three miRs (different from those identified in cells) were common between EVs derived from cells and patients derived-exosomes. These miRs detected in circulating EVs could provide a specific and reliable signature in response to ionizing radiation, which could be useful for monitoring the effectiveness of radiotherapy. Further experiments on a larger patients population with clinical data could also help to define whether this signature might have a prognostic value on the response to radiotherapy.

Published
2021
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