Ovarian cancer glutamine metabolism supports tumor-associated macrophages immune suppression through crosstalk mechanisms

Glutamine metabolism is crucial in epithelial ovarian cancer (EOC). In particular, EOC has been reported as addicted to glutamine metabolism, since its glutaminolytic capacity strongly correlates with cancer aggressiveness and poor prognosis in patients. Furthermore, tumor-associated macrophages (TAMs), key components of the tumor microenvironment (TME) supporting tumor progression and metastasis, possess high glutamine synthetase (GLUL, GS) expression (Figure A), which has been associated with the acquisition of an immunosuppressive phenotype of macrophages in EOC. Recently, we have discovered that N-acetylaspartate (NAA) is released by high glutaminolytic EOC cell lines and its levels in ascitic fluid from EOC patients increase proportionally to cancer stage (Figure B). NAA contributes to the acquisition of an immunosuppressive phenotype of macrophages from PBMCs associated with high-GLUL expression. Overall, the main aim is to dissect the GS-driven crosstalk between EOC and TAMs in the TME.