Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
National Center for Cancer Immune Therapy, Department of Oncology, University Hospital Herlev, Copenhagen, Denmark; Department of Immunology and Microbiology, Inflammation and Cancer Group, University of Copenhagen, Denmark.
Curr Opin Biotechnol. 2023 Dec;84:103008. doi: 10.1016/j.copbio.2023.103008. Epub 2023 Oct 18.
Nucleotide metabolism plays a crucial role in the regulation of the tumor microenvironment (TME) and immune cell function. In the TME, limited availability of nucleotide precursors due to increased consumption by tumor cells and T cells affects both tumor development and immune function. Metabolic reprogramming in tumor cells favors pathways supporting growth and proliferation, including nucleotide synthesis. Additionally, extracellular nucleotides, such as ATP and adenosine, exhibit dual roles in modulating immune function and tumor cell survival. ATP stimulates antitumor immunity by activating purinergic receptors, while adenosine acts as a potent immunosuppressor. Targeting nucleotide metabolism in the TME holds immense promise for cancer therapy. Understanding the intricate relationship between nucleotide metabolism, the TME, and immune responses will pave the way for innovative therapeutic interventions.
核苷酸代谢在肿瘤微环境 (TME) 和免疫细胞功能的调节中起着至关重要的作用。在 TME 中,由于肿瘤细胞和 T 细胞消耗增加,核苷酸前体的有限可用性会影响肿瘤的发展和免疫功能。肿瘤细胞中的代谢重编程有利于支持生长和增殖的途径,包括核苷酸合成。此外,细胞外核苷酸,如 ATP 和腺苷,在调节免疫功能和肿瘤细胞存活方面具有双重作用。ATP 通过激活嘌呤能受体刺激抗肿瘤免疫,而腺苷则是一种有效的免疫抑制剂。针对 TME 中的核苷酸代谢具有巨大的癌症治疗潜力。了解核苷酸代谢、TME 和免疫反应之间的复杂关系将为创新的治疗干预铺平道路。