TY - JOUR
T1 - Fusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1)
AU - Michikawa, Chieko
AU - Gopalakrishnan, Vancheswaran
AU - Harrandah, Amani M.
AU - Karpinets, Tatiana V.
AU - Garg, Rekha Rani
AU - Chu, Randy A.
AU - Park, Yuk Pheel
AU - Chukkapallia, Sasanka S.
AU - Yadlapalli, Nikhita
AU - Erikson-Carter, Kelly C.
AU - Gleber-Netto, Frederico Omar
AU - Sayour, Elias
AU - Progulske-Fox, Ann
AU - Chan, Edward K.L.
AU - Wu, Xiaogang
AU - Zhang, Jianhua
AU - Jobin, Christian
AU - Wargo, Jennifer A.
AU - Pickering, Curtis R.
AU - Myers, Jeffrey N.
AU - Silver, Natalie
N1 - Publisher Copyright:
© 2022
PY - 2022/9
Y1 - 2022/9
N2 - 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.
AB - 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.
KW - Fusobacterium
KW - Head and neck cancer
KW - Microbiome
KW - Oral cancer
KW - PD-L1
KW - Periodontal bacteria
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UR - http://www.scopus.com/inward/citedby.url?scp=85133895419&partnerID=8YFLogxK
U2 - 10.1016/j.neo.2022.100813
DO - 10.1016/j.neo.2022.100813
M3 - Article
C2 - 35834946
AN - SCOPUS:85133895419
SN - 1522-8002
VL - 31
JO - Neoplasia (United States)
JF - Neoplasia (United States)
M1 - 100813
ER -