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:Intratumoral Microbiome: Impact on Cancer Progression and Cellular Immunotherapy.
Intratumoral Microbiome: Impact on Cancer Progression and Cellular Immunotherapy.
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肿瘤内微生物群由肿瘤微环境中的细菌、真菌和病毒组成,可主动影响致癌过程。其关键机制包括诱导宿主DNA损伤、调节WNT/β-catenin、NF-κB和PI3K等重要致癌信号通路,以及协调炎症过程。微生物组与宿主免疫系统的相互作用复杂且双向。一方面,特定微生物可通过抑制细胞毒性T细胞和自然杀伤(NK)细胞活性,或促进肿瘤相关巨噬细胞(TAM)等免疫抑制细胞积累,形成促肿瘤生态位。另一方面,微生物成分可作为T细胞识别的新抗原,或产生代谢物重编程免疫环境、增强抗肿瘤应答。肿瘤内微生物组构成正成为影响免疫治疗结局的重要因素。未来癌症免疫治疗研究应优先采用整合多组学方法开展机制研究,并通过精心设计的临床试验验证微生物生物标志物,系统、循证地开发旨在增强抗肿瘤免疫的微生物组靶向干预措施。
The intratumoral microbiota, comprising bacteria, fungi, and viruses within the tumor microenvironment, actively influences carcinogenesis. Key mechanisms include the induction of host DNA damage, modulation of critical oncogenic signaling pathways such as WNT- -catenin, NF- B, and PI3K, and the orchestration of inflammatory processes. The microbiome's interaction with the host immune system is complex and bidirectional. On one hand, specific microbes can foster a pro-tumorigenic niche by suppressing the activity of cytotoxic T cells and natural killer (NK) cells or by promoting the accumulation of immunosuppressive cell types like tumor-associated macrophages (TAMs).
On the other hand, microbial components can serve as neoantigens for T cell recognition or produce metabolites that reprogram the immune landscape to enhance anti-tumor responses. The composition of this microbiome is emerging as a crucial factor influencing the outcomes of immunotherapies.
Prospective investigations in cancer immunotherapy ought to prioritize mechanistic inquiry employing integrative multi-omics methodologies. The execution of meticulously designed clinical trials for the validation of microbial biomarkers, and the systematic, evidence-based development of microbiome-targeted therapeutic interventions aimed at enhancing antitumor immune responses.
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