Fusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1).

Fusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1).
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梭杆菌在口腔癌中富集,并促进程序性死亡配体1(PD-L1)的诱导。

DOI:
10.1016/j.neo.2022.100813
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发表时间:
2022-09
期刊:
影响因子:
4.8
通讯作者:
Silver, Natalie
Silver, Natalie
中科院分区:
医学2区
文献类型:
--
作者:
Michikawa, Chieko;Gopalakrishnan, Vancheswaran;Harrandah, Amani M.;Karpinets, Tatiana, V;Garg, Rekha Rani;Chu, Randy A.;Park, Yuk Pheel;Chukkapallia, Sasanka S.;Yadlapalli, Nikhita;Erikson-Carter, Kelly C.;Gleber-Netto, Frederico Omar;Sayour, Elias;Progulske-Fox, Ann;Chan, Edward K. L.;Wu, Xiaogan;Zhang, Jianhua;Jobin, Christian;Wargo, Jennifer A.;Pickering, Curtis R.;Myers, Jeffrey N.;Silver, Natalie

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最近,越来越多的研究证明了口腔微生物组与头颈癌发展之间的关系,然而,很少有研究探讨口腔细菌在单个头颈亚位点肿瘤微环境中的作用。在这里,除了对肿瘤样本进行 RNA 测序外,还对 37 名口腔舌鳞状细胞癌 (SCC) 患者的配对肿瘤和邻近正常组织进行了 16S rRNA 基因测序和全外显子组测序 (WES)。我们观察到梭杆菌在口腔舌癌中显着富集,罗氏菌和链球菌在邻近正常组织中富集。与邻近的正常组织相比,肿瘤中的α多样性减少。虽然肿瘤样本中梭杆菌的增加与免疫细胞浸润的变化无关,但与 PD-L1 mRNA 表达的增加有关。因此,我们研究了梭杆菌对头颈 SCC 细胞系中 PD-L1 表达的影响。我们证明,梭杆菌感染可以增加头颈癌细胞系中 PD-L1 mRNA 和表面 PD-L1 蛋白的表达。口腔舌 SCC 中梭杆菌和 PD-L1 表达之间的相关性,以及该细菌在体外诱导 PD-L1 表达的能力,表明梭杆菌在头颈癌肿瘤免疫微环境的调节中具有潜在作用。
Recently, increased number of studies have demonstrated a relationship between the oral microbiome and development of head and neck cancer, however, there are few studies to investigate the role of oral bacteria in the context of the tumor microenvironment in a single head and neck subsite. Here, paired tumor and adjacent normal tissues from thirty-seven oral tongue squamous cell carcinoma (SCC) patients were subjected to 16S rRNA gene sequencing and whole exome sequencing (WES), in addition to RNA sequencing for tumor samples. We observed that Fusobacterium was significantly enriched in oral tongue cancer and that Rothia and Streptococcus were enriched in adjacent normal tissues. A decrease in alpha diversity was found in tumor when compared to adjacent normal tissues. While increased Fusobacterium in tumor samples was not associated with changes in immune cell infiltration, it was associated with increased PD-L1 mRNA expression. Therefore, we examined the effects of Fusobacterium on PD-L1 expression in head and neck SCC cell lines. We demonstrated that infection with Fusobacterium species can increase both PD-L1 mRNA and surface PD-L1 protein expression on head and neck cancer cell lines. The correlation between Fusobacterium and PD-L1 expression in oral tongue SCC, in conjunction with the ability of the bacterium to induce PD-L1 expression in vitro suggests a potential role for Fusobacterium on modulation of the tumor immune microenvironment in head and neck cancer.
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