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 microbiota: roles in cancer initiation, development and therapeutic efficacy.
Intratumoral microbiota: roles in cancer initiation, development and therapeutic efficacy.
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微生物,包括细菌、病毒、真菌和其他真核生物,在人类健康中发挥着关键作用。微生物组的改变可能与复杂疾病相关。在多种肿瘤组织中均发现瘤内微生物组分,且与癌症的发生、发展及治疗疗效密切相关。瘤内微生物群可能通过DNA突变、激活致癌通路、促进慢性炎症、补体系统以及启动转移等机制,促进癌症的发生和进展。
此外,瘤内微生物群不仅可能通过STING信号激活、T细胞和NK细胞激活、TLS产生以及瘤内微生物群衍生抗原呈递等机制增强抗肿瘤免疫,还可能通过上调ROS、促进抗炎环境、T细胞失活和免疫抑制等途径降低抗肿瘤免疫反应并促进癌症进展。瘤内微生物群对抗肿瘤免疫的影响取决于微生物群组成、微生物群与癌症之间的串扰以及癌症状态。瘤内微生物群可能通过不同的信号通路调节癌细胞生理和免疫反应,包括ROS、-catenin、TLR、ERK、NF- B和STING等。这些观点可能有助于将微生物群确定为癌症的诊断或预后评估指标,并作为癌症治疗的新治疗策略和潜在治疗靶点。
Microorganisms, including bacteria, viruses, fungi, and other eukaryotes, play critical roles in human health. An altered microbiome can be associated with complex diseases. Intratumoral microbial components are found in multiple tumor tissues and are closely correlated with cancer initiation and development and therapy efficacy.
The intratumoral microbiota may contribute to promotion of the initiation and progression of cancers by DNA mutations, activating carcinogenic pathways, promoting chronic inflammation, complement system, and initiating metastasis.
Moreover, the intratumoral microbiota may not only enhance antitumor immunity via mechanisms including STING signaling activation, T and NK cell activation, TLS production, and intratumoral microbiota-derived antigen presenting, but also decrease antitumor immune responses and promote cancer progression through pathways including upregulation of ROS, promoting an anti-inflammatory environment, T cell inactivation, and immunosuppression.
The effect of intratumoral microbiota on antitumor immunity is dependent on microbiota composition, crosstalk between microbiota and the cancer, and status of cancers. The intratumoral microbiota may regulate cancer cell physiology and the immune response by different signaling pathways, including ROS, -catenin, TLR, ERK, NF- B, and STING, among others. These viewpoints may help identify the microbiota as diagnosis or prognosis evaluation of cancers, and as new therapeutic strategy and potential therapeutic targets for cancer therapy.
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