L'étude du récepteur ACKR3/CXCR7 dans le glioblastome

After validation of ACKR3 staining by using U87-ACKR3 cell line, we showed that ACKR3 expression was very low in patients GBM stem-like cells. However we detect the receptor on GBM patient tissue, where it appears distributed in various cell subtypes. Both public transcriptomic datasets of GBM and results that we have obtained have revealed that ACKR3 is expressed in tumor cells in situ, but also in cells from the surrounding tumor microenvironment. Morever, ACKR3 expression pattern varies in different regions of a tumor, and between different patients. The role of ACKR3 in GBM growth might be more subtle than expected, and likely involves malignant GBM cells as well as their microenvironment. The role of CXCR4 together with ACKR3 also deserves deep investigation

Patient-Oriented Perspective on Chemokine Receptor Expression and Function in Glioma.

peer reviewedGliomas are severe brain malignancies, with glioblastoma (GBM) being the most aggressive one. Despite continuous efforts for improvement of existing therapies, overall survival remains poor. Over the last years, the implication of chemokines and their receptors in GBM development and progression has become more evident. Recently, large amounts of clinical data have been made available, prompting us to investigate chemokine receptors in GBM from a still-unexplored patient-oriented perspective. This study aims to highlight and discuss the involvement of chemokine receptors-CCR1, CCR5, CCR6, CCR10, CX3CR1, CXCR2, CXCR4, ACKR1, ACKR2, and ACKR3-most abundantly expressed in glioma patients based on the analysis of publicly available clinical datasets. Given the strong intratumoral heterogeneity characterizing gliomas and especially GBM, receptor expression was investigated by glioma molecular groups, by brain region distribution, emphasizing tissue-specific receptor functions, and by cell type enrichment. Our study constitutes a clinically relevant and patient-oriented guide that recapitulates the expression profile and the complex roles of chemokine receptors within the highly diversified glioma landscape. Additionally, it strengthens the importance of patient-derived material for development and precise amelioration of chemokine receptor-targeting therapies

190P Immune-related roles of B7H3 in glioblastoma

editorial reviewe

Nanobody-based retargeting of an oncolytic herpesvirus for eliminating CXCR4+ GBM cells: a proof-of-principle

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, which remains difficult to cure. The very high recurrence rate has been partly attributed to the presence of GBM stem-like cells (GSCs) within the tumors, which have been associated with elevated chemokine receptor 4 (CXCR4) expression. CXCR4 is frequently overexpressed in cancer tissues, including GBM, and usually correlates with a poor prognosis. We have created a CXCR4-retargeted oncolytic herpesvirus (oHSV) by insertion of an anti-human CXCR4 nanobody in glycoprotein D of an attenuated HSV-1 (ΔICP34.5, ΔICP6, and ΔICP47), thereby describing a proof of principle for the use of nanobodies to target oHSVs toward specific cellular entities. Moreover, this virus has been armed with a transgene expressing a soluble form of TRAIL to trigger apoptosis. In vitro, this oHSV infects U87MG CXCR4(+) and patient-derived GSCs in a CXCR4-dependent manner and, when armed, triggers apoptosis. In a U87MG CXCR4(+) orthotopic xenograft mouse model, this oHSV slows down tumor growth and significantly improves mice survival. Customizing oHSVs with diverse nanobodies for targeting multiple proteins appears as an interesting approach for tackling the heterogeneity of GBM, especially GSCs. Altogether, our study must be considered as a proof of principle and a first step toward personalized GBM virotherapies to complement current treatments