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 microbial community profiling identifies clinicomolecular and prognostic subtypes of colorectal cancer liver metastasis.
Intratumoral microbial community profiling identifies clinicomolecular and prognostic subtypes of colorectal cancer liver metastasis.
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肿瘤内微生物群与结直肠癌肝转移(CRLM)有关,但其与临床特征和预后的关系仍有待探索。我们采用5R 16S rRNA基因测序方法,分析了伴和不伴肝转移的结直肠癌患者的肿瘤内微生物群。将CRLM患者分为三种肿瘤内微生物群落亚型(IMCS)。其中包括IMCS1(糖代谢相关肝转移,伴T细胞激活,中等增殖和侵袭能力,中位无病生存期(mDFS)为22个月)、IMCS2(蛋白质代谢相关肝转移,伴NK 细胞激活,高增殖和侵袭能力,mDFS为12个月)和IMCS3(脂质代谢相关肝转移,伴免疫贫乏表型,增殖和侵袭水平最高,mDFS为10个月)。我们的研究确立了肿瘤内微生物组亚型作为CRLM的一种新型风险分层策略,促进了以微生物群为靶点的治疗策略,具有潜在的生存获益。
Intratumoral microbiota are implicated in colorectal cancer liver metastasis (CRLM), but their relationships with clinical characteristics and prognosis remain to be explored. Using 5R 16S rRNA gene sequencing method, we analyzed the intratumoral microbiota of patients with colorectal cancer with and without liver metastasis. CRLM patients were classified into three intratumoral microbial community subtypes (IMCSs).
These included IMCS1 (sugar metabolism-related liver metastasis with T cell activation, moderate proliferation and invasion, and median disease-free survival (mDFS) of 22 months), IMCS2 (protein metabolism-related liver metastasis with natural killer cell activation, high proliferation and invasion, and mDFS of 12 months), and IMCS3 (lipid metabolism-related liver metastasis with a pauci-immune phenotype, the highest level of proliferation and invasion, and mDFS of 10 months).
Our study establishes intratumoral microbiome subtypes as a novel risk stratification strategy for CRLM, facilitating microbiota-directed therapeutic strategies with potential survival benefits.
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