Bioinformatics Core Facility, Department of Biomedicine, University of Basel, Basel, Switzerland; Swiss Institute of Bioinformatics, Basel, Switzerland
Steffen Dettling
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany
Brain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, Switzerland
Sylvia Herter
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zürich, Schlieren, Switzerland
Marina Bacac
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zürich, Schlieren, Switzerland
Gregor Hutter
Brain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, Switzerland; Department of Neurosurgery, University Hospital Basel, Basel, Switzerland
Glioblastoma (GBM) harbors a highly immunosuppressive tumor microenvironment (TME) which influences glioma growth. Major efforts have been undertaken to describe the TME on a single-cell level. However, human data on regional differences within the TME remain scarce. Here, we performed high-depth single-cell RNA sequencing (scRNAseq) on paired biopsies from the tumor center, peripheral infiltration zone and blood of five primary GBM patients. Through analysis of >45,000 cells, we revealed a regionally distinct transcription profile of microglia (MG) and monocyte-derived macrophages (MdMs) and an impaired activation signature in the tumor-peripheral cytotoxic-cell compartment. Comparing tumor-infiltrating CD8+ T cells with circulating cells identified CX3CR1high and CX3CR1int CD8+ T cells with effector and memory phenotype, respectively, enriched in blood but absent in the TME. Tumor CD8+ T cells displayed a tissue-resident memory phenotype with dysfunctional features. Our analysis provides a regionally resolved mapping of transcriptional states in GBM-associated leukocytes, serving as an additional asset in the effort towards novel therapeutic strategies to combat this fatal disease.
