工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Herb-derived immunometabolic modulators: traditional Chinese medicine at the crossroads of metabolism and antitumor immunity.
Herb-derived immunometabolic modulators: traditional Chinese medicine at the crossroads of metabolism and antitumor immunity.
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中医来源的干预措施可以沿着四条汇聚的免疫代谢轴进行系统性定位,这些轴协调肿瘤与免疫系统之间的相互作用。将中医视为一种免疫代谢联合治疗,凸显了其将“冷”肿瘤转化为“热”病灶、加深对化疗、放疗和免疫治疗的应答,并在某些情境下改善治疗耐受性的潜力。未来研究应强调严格的机制解析、标准化且化学定义明确的制剂、生物标志物指导的患者选择,以及设计良好的前瞻性临床试验,以将这种基于轴的框架转化为精准整合肿瘤学。然而,大多数中医来源的免疫代谢干预措施仍未得到完全验证,其转化将需要与轴匹配的生物标志物、严格的安全性评估和前瞻性临床验证。
中医药长期以来在肿瘤学中被用于“扶正祛邪”,但其在现代免疫代谢治疗中的地位仍不明确。目前认为,肿瘤细胞、基质细胞和免疫细胞围绕若干反复出现的代谢轴进行组织,包括糖酵解-乳酸轴、线粒体应激与免疫原性细胞死亡(ICD)轴、脂质-胆汁酸信号轴以及氧化还原平衡轴。阐明基于草药的方剂、分离化合物及现代递送系统如何影响这些代谢轴,可能为将中医药整合到精准癌症治疗中提供机制基础。正文:本叙述性综述将民族药理学知识与药理学及机制研究、基于组学的分析以及新兴纳米医学报告中探讨中医药衍生干预措施在实体瘤中具有明确代谢和免疫结局的研究相结合。我们首先概述肿瘤微环境(TME)的代谢重编程如何塑造主要免疫细胞群,包括树突状细胞(DCs)、CD8⁺ T细胞、肿瘤相关巨噬细胞(TAMs)、髓源性抑制细胞(MDSCs)以及NK/NKT细胞。然后,我们沿四个免疫代谢轴排列代表性的草药衍生药物。在轴I-IV中,多种方剂和单体已被报道可减弱肿瘤糖酵解通量和乳酸负荷,诱导线粒体损伤和与铁死亡相关的ICD,使以脂质-胆汁酸为中心的髓系微环境正常化,并改善DC和T细胞的代谢适应性。例子包括基于黄芪的方剂、葛根芩连汤(GQD)、人参皂苷、小檗碱、甘草查尔酮A、大黄素、雷公藤红素-Rg3和铁基纳米平台、健脾解毒和健脾化瘀汤、复方苦参注射液、复方茯苓颗粒、补中益气汤、咳金炎汤、槐耳、灵芝多糖、参芪益气胶囊,以及负载多糖的囊泡或微针。最后,我们将这些轴线与经典中医理论如扶正祛邪、调肝和脾、培本除浊相联系,提出一个面向临床、基于证候的框架。
Traditional Chinese Medicine (TCM) has long been applied in oncology to "support vital Qi and eliminate pathogenic factors", yet its place within modern immunometabolic therapy is still not clearly defined. Tumor, stromal, and immune cells are now understood to be organized around several recurrent metabolic axes, including glycolysis-lactate, mitochondrial stress and immunogenic cell death (ICD), lipid-bile-acid signaling, and redox balance. Clarifying how herb-based formulas, isolated compounds, and contemporary delivery systems influence these axes may provide a mechanistic foundation for integrating TCM into precision cancer treatment. MAIN BODY: This narrative review brings together ethnopharmacological knowledge with pharmacological and mechanistic studies, omics-based profiling, and emerging nanomedicine reports that examined TCM-derived interventions with defined metabolic and immune outcomes in solid tumors. We first outline how metabolic reprogramming of the tumor microenvironment (TME) shapes major immune populations, including dendritic cells (DCs), CD8⁺ T cells, tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and NK/NKT cells. We then arrange representative herb-derived agents along four immunometabolic axes. Across Axis I-IV, multiple prescriptions and monomers have been reported to attenuate tumor glycolytic flux and lactate burden, induce mitochondrial damage and ferroptosis-linked ICD, normalize lipid-bile-acid-centered myeloid niches, and improve DC and T-cell metabolic fitness. Examples include Astragalus-based formulas, Gegen Qinlian decoction (GQD), ginsenosides, berberine, licochalcone A, emodin, celastrol-Rg3 and iron-based nanoplatforms, Jianpi Jiedu and Jianpi Huayu decoctions, Compound Kushen Injection, Compound Fuling Granule, Hochu-ekki-to, Kejinyan decoction, Huaier, Ganoderma polysaccharides, Shenqi Yiqi Capsule, and polysaccharide-loaded vesicles or microneedles. Finally, we relate these axes to classical TCM doctrines such as Fuzheng Quxie, Tiaogan Hepi, and Peiben Chuzhuo, proposing a clinically oriented, syndrome-informed framework.
TCM-derived interventions can be systematically positioned along four convergent immunometabolic axes that coordinate interactions between tumors and the immune system. Considering TCM as an immunometabolic co-therapy highlights its potential to convert "cold" tumors into "hot" lesions, deepen responses to chemo-, radio- and immunotherapy, and, in some contexts, improve treatment tolerance. Future studies should emphasize rigorous mechanistic dissection, standardized and chemically defined formulations, biomarker-guided patient selection, and well-designed prospective clinical trials to translate this axis-based framework into precision integrative oncology. However, most TCM-derived immunometabolic interventions remain incompletely validated, and their translation will require axis-matched biomarkers, rigorous safety assessment, and prospective clinical validation.
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