Li Shouhua, Han Hengtong, Yang Kaili, Li Xiaoxiao, Ma Libin, Yang Ze, Zhao Yong-Xun
The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China.
The Seventh Department of General Surgery, Department of Thyroid Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China.
Int Immunopharmacol. 2025 Jan 10;144:113702. doi: 10.1016/j.intimp.2024.113702. Epub 2024 Nov 26.
The metabolic reprogramming of cancer cells is a hallmark of many malignancies. To meet the energy acquisition needs of tumor cells for rapid proliferation, tumor cells reprogram their nutrient metabolism, which is caused by the abnormal expression of transcription factors and signaling molecules related to energy metabolic pathways as well as the upregulation and downregulation of abnormal metabolic enzymes, receptors, and mediators. Thyroid cancer (TC) is the most common endocrine tumor, and immunotherapy has become the mainstream choice for clinical benefit after the failure of surgical, endocrine, and radioiodine therapies. TC change the tumor microenvironment (TME) through nutrient competition and metabolites, causing metabolic reprogramming of immune cells, profoundly changing immune cell function, and promoting immune evasion of tumor cells. A deeper understanding of how metabolic reprogramming alters the TME and controls immune cell fate and function will help improve the effectiveness of TC immunotherapy and patient outcomes. This paper aims to elucidate the metabolic communication that occurs between immune cells around TC and discusses how metabolic reprogramming in TC affects the immune microenvironment and the effectiveness of anti-cancer immunotherapy. Finally, targeting key metabolic checkpoints during metabolic reprogramming, combined with immunotherapy, is a promising strategy.
癌细胞的代谢重编程是许多恶性肿瘤的一个标志。为了满足肿瘤细胞快速增殖对能量获取的需求，肿瘤细胞会重新编程其营养代谢，这是由与能量代谢途径相关的转录因子和信号分子的异常表达以及异常代谢酶、受体和介质的上调和下调所导致的。甲状腺癌（TC）是最常见的内分泌肿瘤，在手术、内分泌和放射性碘治疗失败后，免疫疗法已成为实现临床获益的主流选择。甲状腺癌通过营养竞争和代谢产物改变肿瘤微环境（TME），导致免疫细胞的代谢重编程，深刻改变免疫细胞功能，并促进肿瘤细胞的免疫逃逸。更深入地了解代谢重编程如何改变肿瘤微环境并控制免疫细胞的命运和功能，将有助于提高甲状腺癌免疫治疗的有效性和患者的治疗效果。本文旨在阐明甲状腺癌周围免疫细胞之间发生的代谢通讯，并探讨甲状腺癌中的代谢重编程如何影响免疫微环境和抗癌免疫治疗的有效性。最后，在代谢重编程过程中靶向关键代谢检查点，并结合免疫疗法，是一种很有前景的策略。
