Proline metabolism shapes the tumor microenvironment: from collagen deposition to immune evasion

• Published in: Current opinion in biotechnology 2023-12, Vol.84, p.103011-103011, Article 103011
• Main Authors: Kay, Emily J, Zanivan, Sara, Rufini, Alessandro
• Format: Article
• Language: English
• Subjects: Collagen - metabolism; Extracellular Matrix - metabolism; Humans; Immune Evasion; Neoplasms - metabolism; Proline - metabolism; Tumor Microenvironment - physiology
• ISSN: 0958-1669; 1879-0429
• DOI: 10.1016/j.copbio.2023.103011

Proline is a nonessential amino acid, and its metabolism has been implicated in numerous malignancies. Together with a direct role in regulating cancer cells’ proliferation and survival, proline metabolism plays active roles in shaping the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) display high rates of proline biosynthesis to support the production of collagen for the extracellular matrix (ECM). Indeed, impaired proline metabolism in CAFs results in reduced collagen deposition and compromises the growth and metastatic spread of cancer. Moreover, the rate of proline metabolism regulates intracellular reactive oxygen species (ROS) levels, which influence the production and release of cytokines from cancer cells, contributing toward an immune-permissive TME. Hence, targeting proline metabolism is a promising anticancer strategy that could improve patients’ outcome and response to immunotherapy. [Display omitted] •Proline metabolism in CAFs sustains collagen deposition and formation of the ECM in the TME.•Impairing proline metabolism in CAFs decreases collagen deposition and compromises tumor growth.•Proline metabolism controls ROS levels in cells by regulating the NAD(P)+/NAD(P)H ratio.•Regulation of ROS levels by proline metabolism influences cytokine secretion from cancer cells to shape the immune TME.•Targeting proline metabolism in the TME is a promising anticancer avenue.