SCI
12 October 2024
Macrophages and T cells in metabolic disorder-associated cancers
(nature reviews cancer; if=72.5)
Taranto D, Kloosterman DJ, Akkari L.
Correspondence: l.akkari@nki.nl
Cancer and metabolic disorders have emerged as major global health challenges, reaching epidemic levels in recent decades. Often viewed as separate issues, metabolic disorders are shown by mounting evidence to heighten cancer risk and incidence. The intricacies underlying this connection are still being unraveled and encompass a complex interplay between metabolites, cancer cells and immune cells within the tumour microenvironment (TME). Here, we outline the interplay between metabolic and immune cell dysfunction in the context of three highly prevalent metabolic disorders, namely obesity; two associated liver diseases, metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH); and type 2 diabetes. We focus primarily on macrophages and T cells, the critical roles of which in dictating inflammatory response and immune surveillance in metabolic disorder-associated cancers are widely reported. Moreover, considering the ever-increasing number of patients prescribed with metabolism disorder-altering drugs and diets in recent years, we discuss how these therapies modulate systemic and local immune phenotypes, consequently impacting cancer malignancy. Collectively, unraveling the determinants of metabolic disorder-associated immune landscape and their role in fuelling cancer malignancy will provide a framework essential to therapeutically address these highly prevalent diseases.
癌症和代谢紊乱已成为全球健康的主要挑战,近几十年来已达到流行水平。代谢紊乱通常被视为单独的问题,越来越多的证据表明它会增加癌症的风险和发病率。这种联系的复杂性仍在解开,并包括肿瘤微环境(TME)中代谢物、癌症细胞和免疫细胞之间的复杂相互作用。在这里,我们概述了代谢和免疫细胞功能障碍在三种高度流行的代谢疾病背景下的相互作用,即肥胖;两种相关的肝病,代谢功能障碍相关脂肪变性肝病(MASLD)和代谢功能障碍相关的脂肪性肝炎(MASH);以及2型糖尿病。我们主要关注巨噬细胞和T细胞,其在代谢紊乱相关癌症的炎症反应和免疫监视中的关键作用已被广泛报道。此外,考虑到近年来越来越多的患者服用改变代谢紊乱的药物和饮食,我们讨论了这些疗法如何调节全身和局部免疫表型,从而影响癌症恶性肿瘤。总之,揭示代谢紊乱相关免疫景观的决定因素及其在助长癌症恶性肿瘤中的作用,将为治疗这些高度流行的疾病提供一个至关重要的框架。