RT Journal Article
SR Electronic
T1 Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.17.496574
DO 10.1101/2022.06.17.496574
A1 Philip Schmassmann
A1 Julien Roux
A1 Steffen Dettling
A1 Sabrina Hogan
A1 Tala Shekarian
A1 Tomás A. Martins
A1 Marie-Françoise Ritz
A1 Sylvia Herter
A1 Marina Bacac
A1 Gregor Hutter
YR 2022
UL http://biorxiv.org/content/early/2022/06/19/2022.06.17.496574.abstract
AB 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 large-scale dissection of GBM-associated leukocytes, serving as a reference map of human GBM-TME.Competing Interest StatementGregor Hutter has equity in, and is a cofounder of Incephalo Inc. All other authors declare they have no competing interests.