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


METHODS
The immunologic properties of CD44+ cancer stem-like cells were compared with those of CD44- cells using flow cytometry and enzyme-linked immunosorbent assay.


RESULTS
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.


CONCLUSIONS
CSCs might have higher malignant potential with numerous escape strategies from immune attack.
Chikamatsu
Kazuaki
K
Department of Otolaryngology-Head and Neck Surgery, University of Yamanashi, Faculty of Medicine, Chuo, Yamanashi, 409-3898, Japan. chikamatsu@yamanashi.ac.jp
Takahashi
Goro
G
Sakakura
Koichi
K
Ferrone
Soldano
S
Masuyama
Keisuke
K
D015415:Biomarkers / Q000378:metabolism; D002277:Carcinoma / Q000276:immunology / Q000473:pathology; D002294:Carcinoma, Squamous Cell; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D018307:Neoplasms, Squamous Cell / Q000276:immunology / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000276:immunology*; D000077195:Squamous Cell Carcinoma of Head and Neck
D015415:Biomarkers; C497483:CD44 protein, human; D015789:HLA-A2 Antigen; D018960:Hyaluronan Receptors