Patient-based multilevel transcriptome exploration highlights relevant chemokines and chemokine receptor axes in glioblastoma

Abstract

Chemokines and their receptors form a complex interaction network, crucial for precise leukocyte positioning and trafficking. In cancer, they promote malignant cell proliferation and survival but are also critical for immune cell infiltration in the tumor microenvironment. Glioblastoma (GBM) is the most common and lethal brain tumor, characterized by an immunosuppressive TME, with restricted immune cell infiltration. A better understanding of chemokine-receptor interactions is therefore essential for improving tumor immunogenicity. In this study, we assessed the expression of all human chemokines in adult-type diffuse gliomas, with particular focus on GBM, based on patient-derived samples. Publicly available bulk RNA sequencing datasets allowed us to identify the chemokines most abundantly expressed in GBM, with regard to disease severity and across different tumor subregions. To gain insight into the chemokines–receptor network at the single cell resolution, we explored GBmap, a curated resource integrating multiple scRNAseq datasets from different published studies. Our study constitutes the first patient–based handbook highlighting the relevant chemokine–receptor crosstalks, which are of significant interest in the perspective of a therapeutic modulation of the TME in GBM.