CD24 blunts oral squamous cancer development and dampens the functional expansion of myeloid-derived suppressor cells.

ABSTRACTCD24 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 aga...