AUTHOR=Schoeppe Robert , Babl Nathalie , Decking Sonja-Maria , Schönhammer Gabriele , Siegmund Andreas , Bruss Christina , Dettmer Katja , Oefner Peter J. , Frick Linus , Weigert Anna , Jantsch Jonathan , Herr Wolfgang , Rehli Michael , Renner Kathrin , Kreutz Marina 

TITLE=Glutamine synthetase expression rescues human dendritic cell survival in a glutamine-deprived environment

JOURNAL=Frontiers in Oncology

VOLUME=Volume 13 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1120194

DOI=10.3389/fonc.2023.1120194

ISSN=2234-943X

ABSTRACT=Glutamine deficiency is a well-known feature of the tumor environment. Here we analyzed the impact of glutamine deprivation on human myeloid cell survival and function. The absence of extracellular glutamine only slightly affected postmitotic human monocyte to dendritic cell (DC) differentiation, function and survival. Similar results were obtained for monocyte-derived macrophages. In contrast, proliferation of the monocytic leukemia cell line THP-1 was significantly suppressed. While macrophages exhibited high constitutive glutamine synthetase (GS) expression, glutamine deprivation induced GS in DC and THP-1. Accordingly, proliferation of THP-1 was rescued by addition of the GS substrate glutamate and 13C tracing analyses revealed conversion of glutamate to glutamine. Supplementation with L-methionine-S-sulfoximine (MSO), an irreversible GS inhibitor, reduced the survival of DC and macrophages and counteracted the proliferation rescue of THP-1 by glutamate. Our results show that GS supports myeloid cell survival in a glutamine poor environment. Notably, in addition to suppressing proliferation and survival of tumor cells, the blockade of GS also targets immune cells such as DCs and macrophages.