Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation

Schmassmann, P.; Roux, J.; Dettling, S.; Hogan, S.; Shekarian, T.; Martins, T. A.; Ritz, M.-F.; Herter, S.; Bacac, M.; Hutter, G.

doi:10.1101/2022.06.17.496574

bioRxiv · 10.1101/2022.06.17.496574

Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation

Schmassmann, P.·Roux, J.·Dettling, S.·Hogan, S.·Shekarian, T.·Martins, T. A.·Ritz, M.-F.·Herter, S.·Bacac, M.·Hutter, G.

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Abstract

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 > 45000 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.

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Schmassmann, P., Roux, J., Dettling, S., Hogan, S., Shekarian, T., Martins, T. A., Ritz, M.-F., Herter, S., Bacac, M., Hutter, G.. 2022-06-19. Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation. https://doi.org/10.1101/2022.06.17.496574

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