Abstract
Simple SummaryChemokines and their receptors have been pointed out as key actors in a variety of human cancers, playing pivotal roles in multiples processes and pathways. The present study aims at deciphering the functions of several chemokine receptors in gliomas, starting from publicly available patient-derived transcriptomic data with support from the current literature in the field, and sheds light on the clinical relevance of chemokine receptors in targeted therapeutic approaches for glioma patients.Gliomas 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.
Highlights
Gliomas are glial tumors of the central nervous system (CNS), which are categorized into different subtypes and clinical grades based on their histological features as well as molecular markers (according to the World Health Organization (WHO)) [1]
We looked into the expression of CCR1, CCR5, CCR6, CCR10, CX3C receptor 1 (CX3CR1), CXCR2, CXCR4, ACKR1, ACKR2 and
This study reported that glioma cells overexpress CX3CL1, which is responsible for the recruitment of CX3CR1-expressing microglia and macrophages
Summary
Gliomas are glial tumors of the central nervous system (CNS), which are categorized into different subtypes and clinical grades based on their histological features as well as molecular markers (according to the World Health Organization (WHO)) [1]. Several mechanisms underlie tumor relapse: (1) the infiltrative nature of GBM that invades and disseminates through the whole brain tissue [5]; (2) the multilevel heterogeneity of GBM tumors, which exhibit inter-patient and intra-tumoral disparities [6], include diverse cell types and cellular states [7]; and (3) the ability of GBM cells to interact with and adapt to their microenvironment [8], to interconnect with neighboring tumor cells [9] or to harness healthy brain cells [10]
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