Immunoregulatory properties of CD44+ cancer stem-like cells in squamous cell carcinoma of the head and neck.

Abstract

CD44 was found as a surface marker in cancer stem cell (CSC) of squamous cell carcinoma of the head and neck (SCCHN); however, the immunologic properties of such CSCs have not yet been elucidated. The immunologic properties of CD44+ cancer stem-like cells were compared with those of CD44- cells using flow cytometry and enzyme-linked immunosorbent assay. CD44+ cells exhibited weak HLA-A2 and class II expression. Interestingly, downregulation of transporter antigen processing (TAP)2 was found in CD44+ cells. The CD44+ cell population produced significantly higher levels of interleukin (IL)-8, granulocyte colony-stimulating factor (G-CSF), and transforming growth factor (TGF)-β than the CD44- cell population. Moreover, CD44+ cells have been shown to not only more strongly inhibit T-cell proliferation, but also to more efficiently inhibit regulatory T cells (Treg cells) and myeloid-derived suppressor cells (MDSC) as compared with CD44- cells. Additionally, CD44+ cells suppressed Th1 responses and enhanced regulatory T cell responses. CSCs might have higher malignant potential with numerous escape strategies from immune attack.