Holbert Cassandra E, Casero Robert A, Stewart Tracy Murray
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Discov Oncol. 2024 May 18;15(1):173. doi: 10.1007/s12672-024-01034-9.
Cellular proliferation, function and survival is reliant upon maintaining appropriate intracellular polyamine levels. Due to increased metabolic needs, cancer cells elevate their polyamine pools through coordinated metabolism and uptake. High levels of polyamines have been linked to more immunosuppressive tumor microenvironments (TME) as polyamines support the growth and function of many immunosuppressive cell types such as MDSCs, macrophages and regulatory T-cells. As cancer cells and other pro-tumorigenic cell types are highly dependent on polyamines for survival, pharmacological modulation of polyamine metabolism is a promising cancer therapeutic strategy. This review covers the roles of polyamines in various cell types of the TME including both immune and stromal cells, as well as how competition for nutrients, namely polyamine precursors, influences the cellular landscape of the TME. It also details the use of polyamines as biomarkers and the ways in which polyamine depletion can increase the immunogenicity of the TME and reprogram tumors to become more responsive to immunotherapy.
细胞增殖、功能及存活依赖于维持适当的细胞内多胺水平。由于代谢需求增加，癌细胞通过协调代谢和摄取来提高其多胺库。高水平的多胺与更多免疫抑制性肿瘤微环境（TME）相关，因为多胺支持许多免疫抑制细胞类型（如骨髓来源的抑制细胞、巨噬细胞和调节性T细胞）的生长和功能。由于癌细胞和其他促肿瘤细胞类型高度依赖多胺来存活，多胺代谢的药理学调节是一种有前景的癌症治疗策略。本综述涵盖了多胺在TME的各种细胞类型（包括免疫细胞和基质细胞）中的作用，以及对营养物质（即多胺前体）的竞争如何影响TME的细胞格局。它还详细介绍了多胺作为生物标志物的用途，以及多胺消耗可增加TME免疫原性并使肿瘤重编程以对免疫疗法更敏感的方式。
