Fusobacterium Is Enriched in Oral Cancer and Promotes Induction of Programmed Death-Ligand 1 (Pd-L1)

Authors

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 Myers
Natalie Silver

Publication Date

9-1-2022

Journal

Neoplasia

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.

Keywords

B7-H1 Antigen, Carcinoma, Squamous Cell, Fusobacterium, Head and Neck Neoplasms, Humans, Mouth Neoplasms, RNA, Messenger, RNA, Ribosomal, 16S, Squamous Cell Carcinoma of Head and Neck, Tongue Neoplasms, Tumor Microenvironment

DOI

10.1016/j.neo.2022.100813

PMID

35834946

PMCID

PMC9287628

PubMedCentral® Posted Date

7-11-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes