RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Microbiome-guided cancer immunotherapy: immune mechanisms, resistance pathways, and translational opportunities for precision oncology.
Microbiome-guided cancer immunotherapy: immune mechanisms, resistance pathways, and translational opportunities for precision oncology.
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肠道微生物组日益被认为是肿瘤-免疫相互作用的调节因子,并与癌症的发生、发展和治疗反应相关,而直接因果证据在机制性和干预性模型中最为有力。微生物组成和代谢物,包括 SCFAs、胆汁酸、肌苷和色氨酸衍生代谢产物,可能通过影响肿瘤微环境(TME)和全身免疫反应来塑造宿主免疫,尽管证据强度因模型系统和临床背景而异。这些微生物信号已被发现与 T 细胞、B 细胞、NK 细胞和 MDSCs 的变化相关,机制性研究支持其对细胞因子网络、免疫检查点信号、炎症和抗肿瘤免疫的影响。新兴的转化证据表明,特定微生物特征可能作为免疫治疗疗效、耐药和治疗相关毒性的预测性生物标志物。与此同时,微生物组靶向策略,包括 FMT、益生菌、益生元、饮食调节和工程化微生物治疗,正在被研究作为改善癌症治疗的辅助方法,但其临床疗效仍未得到完全验证。
因此,理解微生物组-免疫串扰可能通过识别可操作的微生物靶点来支持精准肿瘤学,从而改善治疗结局、克服免疫介导的治疗耐药,并在临床肿瘤学实践中指导不同癌症类型和场景下的患者分层。
The gut microbiome is increasingly recognized as a modulator of tumor-immune interactions and has been associated with cancer development, progression, and therapeutic response, while direct causal evidence remains strongest in mechanistic and interventional models. Microbial composition and metabolites, including SCFAs, bile acids, inosine, and tryptophan-derived products, may shape host immunity by influencing the tumor microenvironment (TME) and systemic immune responses, although the strength of evidence varies by model system and clinical context. These microbial signals have been linked to changes in T cells, B cells, NK cells, and MDSCs, with mechanistic studies supporting effects on cytokine networks, immune checkpoint signaling, inflammation, and antitumor immunity.
Emerging translational evidence indicates that specific microbial signatures may serve as predictive biomarkers for immunotherapy efficacy, resistance, and treatment-related toxicity. In parallel, microbiome-targeted strategies, including FMT, probiotics, prebiotics, dietary modulation, and engineered microbial therapeutics, are being investigated as adjunctive approaches to improve cancer therapy, but their clinical efficacy remains incompletely validated.
Understanding microbiome-immune crosstalk may therefore support precision oncology by identifying tractable microbial targets for improving therapeutic outcomes, overcoming immune-mediated treatment resistance, and guiding patient stratification across diverse cancer types and settings in clinical oncology practice.
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