METABOLOMIC INSIGHTS INTO THE METABOLIC INTERPLAY IN THE TUMOR MICROENVIRONMENT

The metabolic crosstalk between tumor and immune cells in the tumor microenvironment (TME) has emerged as a critical contributor to cancer progression and response to therapy. Macrophages are abundant innate immune cells in the TME, which may have anti-tumoral functions or, instead, acquire an immune-suppressive, tumor-supportive phenotype. It is becoming increasingly evident that the functional behavior of tumor-associated macrophages (TAM) heavily depends on their ability to reprogram intracellular metabolism in response to different microenvironmental stimuli. Hence, it is important to characterize the metabolic plasticity of TAMs and its implications for tumor development. In this work, we employ NMR metabolomics to elucidate how in vitro generated tumor-educated macrophages (TEM) adapt their metabolism and shift their phenotype in response to the metabolic conditions imposed by different breast cancer (BC) cell subtypes. Potentially important nutritional exchanges and immunoregulatory metabolites in the BC TME are revealed and discussed.