There is increasing evidence in certain malignancies that tumor cells are organized into a hierarchy originating from a small population of cancer stem cells (CSCs) that possesses extensive proliferative and self-renewal potential, and that these CSCs are responsible for maintaining the tumors. In squamous cell carcinoma of the head and neck (SCCHN), CD44+ cells with significant tumorigenic potential have been identified as CSCs; however, the immunological properties of such CSCs have not yet been elucidated. In this study, we investigated the immunological functions of CD44+ cells from a SCCHN cell line. Analysis of flow cytometry demonstrated that the expression of HLA-A2 molecules was deficient in the parental cell line, whereas the CD44+ cell population restored HLA-A2 expression, although at very low levels. Moreover, CD44+ cells exhibited weak HLA class II expression on the cell surface. Interestingly, down-regulation of TAP2 was found in CD44+ cells. The CD44+ cell population produced significantly higher levels of IL-8, G-CSF, and TGF-β than the CD44- cell population. Moreover, CD44+ cells have been shown to not only more strongly inhibit the proliferation of T cells activated with anti-CD3/CD28 mAb, but also to more efficiently induce CD4+CD25+FOXP3+ Treg cells and myeloid-derived suppressor cells as compared with CD44- cells. Additionally, CD44+ cells also suppressed Th1 responses (IFN-γ production by PBMCs) and enhanced regulatory T cell responses (IL-10 production by PBMCs). Thus, CSCs may have higher immunosuppressive ability promoting evasion from immunosurveillance; therefore, the development of novel immunotherapeutic strategies to efficiently overcome CSCs-driven immune suppression is urgently needed.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5314.