Natural Compounds as Metabolic Modulators of the Tumor Microenvironment

The tumor microenvironment (TME) is a heterogenous assemblage of malignant and non-malignant cells, including infiltrating immune cells and other stromal cells, together with extracellular matrix and a variety of soluble factors. This complex and dynamic milieu strongly affects tumor differentiation, progression, immune evasion, and response to therapy, thus being an important therapeutic target. The phenotypic and functional features of the various cell types present in the TME are largely dependent on their ability to adopt different metabolic programs. Hence, modulating the metabolism of the cells in the TME, and their metabolic crosstalk, has emerged as a promising strategy in the context of anticancer therapies. Natural compounds offer an attractive tool in this respect as their multiple biological activities can potentially be harnessed to '(re)-educate' TME cells towards antitumoral roles. The present review discusses how natural compounds shape the metabolism of stromal cells in the TME and how this may impact tumor development and progression.

Automated summary

The tumor microenvironment consists of a complex interplay of malignant and non-malignant cells, immune cells, stromal cells, extracellular matrix, and soluble factors, which strongly affect tumor progression and response to therapy. Modulating the metabolism of cells in the TME has emerged as a promising strategy in anticancer therapies. Natural compounds show potential in reshaping the metabolism of stromal cells in the TME towards anti-tumoral roles.