Insights into the tumor-stromal-immune cell metabolism cross talk in ovarian cancer.

The ovarian cancer tumor microenvironment (TME) consists of a constellation of abundant cellular components, extracellular matrix, and soluble factors. Soluble factors, such as cytokines, chemokines, structural proteins, extracellular vesicles, and metabolites, are critical means of noncontact cellular communication acting as messengers to convey pro- or antitumorigenic signals. Vast advancements have been made in our understanding of how cancer cells adapt their metabolism to meet environmental demands and utilize these adaptations to promote survival, metastasis, and therapeutic resistance. The stromal TME contribution to this metabolic rewiring has been relatively underexplored, particularly in ovarian cancer. Thus, metabolic activity alterations in the TME hold promise for further study and potential therapeutic exploitation. In this review, we focus on the cellular components of the TME with emphasis on 1) metabolic signatures of ovarian cancer; 2) understanding the stromal cell network and their metabolic cross talk with tumor cells; and 3) how stromal and tumor cell metabolites alter intratumoral immune cell metabolism and function. Together, these elements provide insight into the metabolic influence of the TME and emphasize the importance of understanding how metabolic performance drives cancer progression.