Metabolites and the tumour microenvironment: from cellular mechanisms to systemic metabolism

The tumour microenvironment (TME) is a unique cellular and metabolic landscape. Elia and Haigis describe how metabolism influences, and is affected by, the complexity of cellular interactions within the TME and highlight opportunities for therapeutic intervention. Metabolic transformation is a hallmark of cancer and a critical target for cancer therapy. Cancer metabolism and behaviour are regulated by cell-intrinsic factors as well as metabolite availability in the tumour microenvironment (TME). This metabolic niche within the TME is shaped by four tiers of regulation: (1) intrinsic tumour cell metabolism, (2) interactions between cancer cells and non-cancerous cells, (3) tumour location and heterogeneity and (4) whole-body metabolic homeostasis. Here, we define these modes of metabolic regulation and review how distinct cell types contribute to the metabolite composition of the TME. Finally, we connect these insights to understand how each of these tiers offers unique therapeutic potential to modulate the metabolic profile and function of all cells inhabiting the TME.

Automated summary

The article provides a detailed examination of the complexity of cellular metabolism within the tumor microenvironment, along with potential therapeutic intervention opportunities. Cancer cell metabolism and behavior are regulated by multiple factors, and the metabolic environment within the TME is influenced by various tiers. Understanding the interactions of these tiers reveals unique therapeutic potential for modulating the metabolic profile and function of all cells in the TME.