Transcriptome Analysis Identifies Accumulation of Natural Killer Cells with Enhanced Lymphotoxin-β Expression during Glioblastoma Progression

Monaco G, Khavaran A, Gasull AD, Cahueau J, Diebold M, Chhatbar C, Friedrich M, Heiland DH, Sankowski R (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Cancers MDPI

Book Volume: 14

Article Number: 4915

Journal Issue: 19

DOI: 10.3390/cancers14194915

Abstract

Glioblastomas are the most common primary brain tumors. Despite extensive clinical and molecular insights into these tumors, the prognosis remains dismal. While targeted immunotherapies have shown remarkable success across different non-brain tumor entities, they failed to show efficacy in glioblastomas. These failures prompted the field to reassess the idiosyncrasies of the glioblastoma microenvironment. Several high-dimensional single-cell RNA sequencing studies generated remarkable findings about glioblastoma-associated immune cells. To build on the collective strength of these studies, we integrated several murine and human datasets that profiled glioblastoma-associated immune cells at different time points. We integrated these datasets and utilized state-of-the-art algorithms to investigate them in a hypothesis-free, purely exploratory approach. We identified a robust accumulation of a natural killer cell subset that was characterized by a downregulation of activation-associated genes with a concomitant upregulation of apoptosis genes. In both species, we found a robust upregulation of the Lymphotoxin-β gene, a cytokine from the TNF superfamily and a key factor for the development of adaptive immunity. Further validation analyses uncovered a correlation of lymphotoxin signaling with mesenchymal-like glioblastoma regions in situ and in TCGA and CGGA glioblastoma cohorts. In summary, we identify lymphotoxin signaling as a potential therapeutic target in glioblastoma-associated natural killer cells.

Authors with CRIS profile

Dieter Henrik Heiland

Involved external institutions

Albert-Ludwigs-Universität Freiburg DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE)

How to cite

APA:

Monaco, G., Khavaran, A., Gasull, A.D., Cahueau, J., Diebold, M., Chhatbar, C.,... Sankowski, R. (2022). Transcriptome Analysis Identifies Accumulation of Natural Killer Cells with Enhanced Lymphotoxin-β Expression during Glioblastoma Progression. Cancers, 14(19). https://doi.org/10.3390/cancers14194915

MLA:

Monaco, Gianni, et al. "Transcriptome Analysis Identifies Accumulation of Natural Killer Cells with Enhanced Lymphotoxin-β Expression during Glioblastoma Progression." Cancers 14.19 (2022).

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