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

Chieko Michikawa, Vancheswaran Gopalakrishnan, Amani M. Harrandah, Tatiana V. Karpinets, Rekha Rani Garg, Randy A. Chu, Yuk Pheel Park, Sasanka S. Chukkapallia, Nikhita Yadlapalli, Kelly C. Erikson-Carter, Frederico Omar Gleber-Netto, Elias Sayour, Ann Progulske-Fox, ‏Edward K.L. Chan, Xiaogang Wu, Jianhua Zhang, Christian Jobin, Jennifer A. Wargo, Curtis R. Pickering, Jeffrey N. MyersNatalie Silver

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number100813
JournalNeoplasia (United States)
Volume31
DOIs
StatePublished - Sep 2022
Externally publishedYes

Keywords

  • Fusobacterium
  • Head and neck cancer
  • Microbiome
  • Oral cancer
  • PD-L1
  • Periodontal bacteria

ASJC Scopus subject areas

  • Cancer Research

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