title: CD24 blunts oral squamous cancer development and dampens the functional expansion of myeloid-derived suppressor cells.
abstract: CD24 expression has been implicated in the oncogenesis of multiple types of cancer and high tumor expression is considered a poor prognosis factor; however, the role of CD24 in oral cancer progression is unknown. Unlike other cancer types, we found that higher CD24 levels in human oral cancers are correlated to lower clinical stage and better overall survival. We then dissected the role of CD24 and mechanisms in oral cancer pathogenesis in mice using a genetic strategy and demonstrated that CD24 deficiency increased the oral cavity tumor burden in response to the carcinogen 4-nitroquioline 1-oxide (4-NQO). Immune profile analysis showed a significant expansion as well as increased suppressive function of myeloid-derived suppressor cells (MDSCs) in CD24-/-mice, but no apparent impairment in T cells, B cells, or dendritic cells. Further, studies with an orthotopically transplanted syngeneic squamous carcinoma model in the tongue of CD24-/-and CD24+/-mice confirmed the protective roles of CD24 against cancer. Moreover, the difference in tumor growth between CD24-/-and CD24+/-mice was blunted by immunodepletion of MDSCs. We conclude that CD24 expression impedes MDSC expansion and function, and thus slows oral cancer oncogenesis. This study is the first to examine the role of CD24 in ade novooral cancer model, and it highlights the need to consider the immune regulatory roles of CD24 in the development of CD24-targeted therapy for cancer.
authors.affiliation: Department of Microbiology & Immunology, Medical University of South Carolina , Charleston, SC, USA.
authors.forename: Caroline W
authors.initials: CW
authors.lastname: Fugle
authors.affiliation: Department of Microbiology & Immunology, Medical University of South Carolina , Charleston, SC, USA.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Microbiology & Immunology, Medical University of South Carolina , Charleston, SC, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Hong
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical University of South Carolina , Charleston, SC, USA.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Oral Health Sciences, Medical University of South Carolina , Charleston, SC, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Westwater
authors.affiliation: Department of Oral Health Sciences, Medical University of South Carolina , Charleston, SC, USA.
authors.forename: Saleh
authors.initials: S
authors.lastname: Rachidi
authors.affiliation: Department of Oral Health Sciences, Medical University of South Carolina , Charleston, SC, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina , Charleston, SC, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garret-Mayer
authors.affiliation: Department of Oral Health Sciences, Medical University of South Carolina , Charleston, SC, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Kirkwood
authors.affiliation: Department of Microbiology & Immunology, Medical University of South Carolina , Charleston, SC, USA.
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Microbiology & Immunology, Medical University of South Carolina , Charleston, SC, USA.
authors.forename: Zihai
authors.initials: Z
authors.lastname: Li
keywords: 4NQO; CD24; HNSCC; HSA; myeloid-derived suppressor cell (MDSC); oral cancer