色氨酸代谢重编程驱动肿瘤免疫逃逸的机制及中药增敏免疫治疗的研究进展

doi:10.3969/j.issn.1006-5725.2026.09.006

Abstract

Abstract:

As a crucial hub that links immune dysregulation and tumor progression， tryptophan metabolism has emerged as a transdisciplinary frontier in cancer research. This review initially delineates the functional heterogeneity of tryptophan-catabolizing enzymes and their molecular pathways that govern immune cell dynamics in the tumor microenvironment （TME） through dual mechanisms： tryptophan depletion and kynurenine （KYN） accumulation. Subsequently， by concentrating on the metabolic characteristics of breast cancer， colorectal cancer， glioma， and epithelial ovarian cancer， we systematically analyze the histotype-specific reprogramming of tryptophan metabolism. Finally， we assess the regulatory effects of traditional Chinese medicine （TCM） active ingredients （monomers and compound formulas） on reshaping the TME by targeting tryptophan metabolic pathways. This review aims to offer mechanistic and translational insights for surmounting tumor metabolic adaptation barriers and enhancing immunotherapy efficacy.

Key words: tryptophan metabolic reprogramming, kynurenine pathway, indoleamine 2，3-dioxygenase 1, tumor immune escape, programmed death-ligand 1, immune sensitization therapy of traditional Chinese medicine

CLC Number:

R730.23

Wenjie ZHANG,Shuo SUN,Zhiyue REN,Yumeng GONG,Youzhi SUN,Yi ZHAO. Research advances in mechanisms of tryptophan metabolic reprogramming-driven tumor immune escape and immune sensitization therapy of traditional chinese medicine[J]. The Journal of Practical Medicine, 2026, 42(9): 1525-1535.

Figures/Tables 2

Fig.1

Tab.1

Summary of studies on antitumor activity of traditional Chinese medicine active ingredients via regulating tryptophan metabolism pathway"

分类	中药有效成分	癌症类型	机制	参考文献
黄酮类	MY	肺癌	降低IDO1的表达水平，同时减少由IDO1催化产生的异丙氨酸	[58]
	ISL	TNBC	下调IRF5并干扰SLC7A5/IDO1介导的TRP代谢	[63]
	槲皮素	胃癌	抑制IDO1介导的TRP代谢，发挥抗增生和抗迁移作用	[66]
	苦参醇A	NSCLC	靶向抑制IDO1，并且能够增强非小细胞肺癌对放射治疗的敏感性	[71]
多糖类	GPs	NSCLC	调节肠道微生物群和KYN/TRP的比例，增强抗PD-1/PD-L1免疫疗效	[72]
	GLP	CRC	降低血清中KYN/TRP的比例，促进T细胞的抗肿瘤免疫	[75]
	GLP	肺癌	调控CARD9-NF-κB-IDO途径，抑制MDSCs的积累	[76]
	岩藻多糖	乳腺癌	干预TRP代谢，改善效应T细胞功能并抑制Treg细胞的产生	[78]
	岩藻多糖	肝细胞癌	调控肠道微生物，降低IDO1的表达	[79]
	APS	肺癌、黑色素瘤	上调肿瘤细胞中Cx43的表达，从而下调IDO1的转录	[80]
	APS	结肠癌	抑制肿瘤微环境中IDO1的表达，增加CD8? T淋巴细胞浸润	[81]
萜类	PNS	CRC	抑制STAT1介导的IDO1表达，缓解肿瘤微环境中Treg细胞的免疫抑制	[84]
	丹参酮	TNBC	抑制IDO1和TDO的激活，干预KP，经由Bcl-2/Bax途径促进其凋亡	[87]
	丹参酮	CRC	双重阻断IDO1和TDO2，增强抗PD-1治疗效果	[88]
	CBD	前列腺癌	通过靶向TRP分解，降低了癌细胞中IDO1和AhR的表达	[90]
	CBD	GBM	降低IDO、PD-L1和Ki67表达	[91]
	AS	肺癌	抑制IDO表达，下调Tregs、上调细胞毒性T淋巴细胞功能	[94]
		子宫平滑肌瘤	可能抑制IDO1激活PTEN/PI3K/AKT信号，促进肿瘤细胞凋亡	[95]
		白血病	双重抑制IDO1和TDO2，阻断TRP代谢	[96]
生物碱类	蝙蝠葛碱	膀胱癌	通过HCK/IDO1轴干扰M2型TAMs	[97]
木脂素类	厚朴酚	NSCLC	剂量依赖性下调IDO-1、VEGF和FOXP3，诱导凋亡和细胞周期阻滞	[101]
木脂素类	厚朴酚	结肠癌	双重靶向抑制肿瘤抑制因子p53及TRP代谢吲哚途径	[102]

Tab.1

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Research advances in mechanisms of tryptophan metabolic reprogramming-driven tumor immune escape and immune sensitization therapy of traditional chinese medicine

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