期刊
FRONTIERS IN IMMUNOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.01720
关键词
immunometabolism; metabolic reprogramming; immune cell regulation; NAD; tumor microenvironment
类别
资金
- Italian Institute for Genomic Medicine Institutional funds
- Gilead Fellowship program 2018
- Ministry of Education University and ResearchMIUR, PRIN Project [2017CBNCYT]
- Progetto strategico di Eccellenza Dipartimentale [D15D18000410001]
- ITN INTEGRATA program [813284]
Cancer cells, particularly in solid tumors, are surrounded by non-neoplastic elements, including endothelial and stromal cells, as well as cells of immune origin, which can support tumor growth by providing the right conditions. On the other hand, local hypoxia, and lack of nutrients induce tumor cells to reprogram their metabolism in order to survive, proliferate, and disseminate: the same conditions are also responsible for building a tumor-suppressive microenvironment. In addition to tumor cells, it is now well-recognized that metabolic rewiring occurs in all cellular components of the tumor microenvironment, affecting epigenetic regulation of gene expression and influencing differentiation/proliferation decisions of these cells. Nicotinamide adenine dinucleotide (NAD) is an essential co-factor for energy transduction in metabolic processes. It is also a key component of signaling pathways, through the regulation of NAD-consuming enzymes, including sirtuins and PARPs, which can affect DNA plasticity and accessibility. In addition, both NAD-biosynthetic and NAD-consuming enzymes can be present in the extracellular environment, adding a new layer of complexity to the system. In this review we will discuss the role of the NADome in the metabolic cross-talk between cancer and infiltrating immune cells, contributing to cancer growth and immune evasion, with an eye to therapeutic implications.
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