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:Reduced Abundance of Phocaeicola in Mucosa-associated Microbiota Is Associated with Distal Colorectal Cancer Metastases Possibly through an Altered Local Immune Environment.
Reduced Abundance of Phocaeicola in Mucosa-associated Microbiota Is Associated with Distal Colorectal Cancer Metastases Possibly through an Altered Local Immune Environment.
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Phocaeicola 的相对减少削弱了远端 CRC 的局部抗肿瘤免疫反应,这可能促进转移扩散。
本研究的目的是识别在远端结直肠癌(CRC)转移过程中,其肿瘤区域减少与转移过程相关的微生物群。
连续纳入28例在我院接受手术切除的远端CRC患者。采用16S核糖体核糖核酸基因扩增子测序分析28份手术切除结直肠癌标本中的微生物群,并评估微生物群的相对丰度(RA)。通过免疫组织化学方法评估结直肠癌中TIL(肿瘤浸润淋巴细胞)和肿瘤相关巨噬细胞(TAM)的密度。
Phocaeicola是正常黏膜中最丰富的微生物群。肿瘤组织中Phocaeicola的RA倾向于低于正常黏膜,尽管差异不显著(p=0.0732)。肿瘤部位Phocaeicola的RA与肿瘤浸润深度(pT-stage)或肿瘤大小均无相关性,但在有淋巴结转移的患者中显著降低(p<0.05),在有远处转移的患者中也显著降低(p<0.001)。肿瘤部位Phocaeicola的RA与CD3(+)或CD8(+) TIL的密度呈正相关。由于P. vulgatus是Phocaeicola中最优势的菌种(47%),因此也研究了P. vulgatus的RA与CRC转移及其与TIL和TAM的关联。P. vulgatus表现出与Phocaeicola属相似的趋势,但无统计学显著性。
The aim of this study was to identify the microbiota whose decrease in tumor area was associated with the metastatic process of distal colorectal cancer (CRC).
Twenty-eight consecutive patients with distal CRC undergoing surgical resection in our hospital were enrolled. Microbiota in 28 specimens from surgically resected colorectal cancers were analyzed using 16S ribosomal ribonucleic acid gene amplicon sequencing and the relative abundance (RA) of microbiota was evaluated. The densities of tumor-infiltrating lymphocytes (TIL) and tumor associated macrophages (TAM) in the colorectal cancers were immunohistochemically evaluated.
Phocaeicola was the most abundant microbiota in normal mucosa. The RA of Phocaeicola in tumor tissues tended to be lower than that in normal mucosa although the difference was not significant (p=0.0732). The RA of Phocaeicola at tumor sites did not correlate either with depth of tumor invasion (pT-stage) or tumor size, however they were significantly reduced in patients with nodal metastases (p<0.05) and those with distant metastases (p<0.001). The RA of Phocaeicola at tumor sites showed positive correlation with the densities of CD3(+) or CD8(+) TIL. Since P. vulgatus was the most dominant species (47%) of the Phocaeicola , the RA of P. vulgatus and CRC metastasis and its association with TIL and TAM were also investigated. P. vulgatus showed a similar trend to genus Phocaeicola but was not statistically significant.
A relative reduction of Phocaeicola attenuates the local anti-tumor immune response in distal CRC, which may facilitate metastatic spread.
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