Metabolism shapes the tumor microenvironment

•Differential vasculature perfusion and oncogenic load promote tumor metabolic heterogeneity.•Activated cancer associated fibroblasts and pancreatic stellate cells supply nutrients to foster tumor growth.•Opposing cell-dependent functions in the tumor microenvironment promoted by different signaling routes.•Tumor metabolic activity halts efficient immune responses.

Tumors are strongly influenced by the surrounding normal tissue, which forms a specialized niche termed the tumor microenvironment (TME). The TME is modeled by cancer cells for their own benefit through a complex array of interactions. The identification of new forms of communication within the TME, which are dependent on the tumor's metabolic activity, has expanded our understanding of this heterocellular regulation and has revealed potential therapeutic targets. This review will summarize recent findings on the metabolic regulation of tumor cells by the TME. The concepts to be discussed include the existence of metabolic intratumoral heterogeneity, the contribution of cancer associated fibroblasts (CAFs) to tumor progression, and the regulation of tumor immunology by tumor-secreted metabolites.

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