Cytotoxic T Lymphocytes Efficiently Recognize Human Colon Cancer Stem-Like Cells

Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
American Journal Of Pathology (Impact Factor: 4.59). 04/2011; 178(4):1805-13. DOI: 10.1016/j.ajpath.2011.01.004
Source: PubMed


Cancer stem-like cells (CSCs) and tumor-initiating cells (TICs) are a small population of cancer cells that share three properties: tumor initiating ability, self-renewal, and differentiation. These properties suggest that CSCs/TICs are essential for tumor maintenance, recurrence, and distant metastasis. Here, we show that cytotoxic T lymphocytes (CTLs) specific for the tumor-associated antigen CEP55 can efficiently recognize colon CSCs/TICs both in vitro and in vivo. Using Hoechst 33342 dye staining, we isolated CSCs/TICs as side population (SP) cells from colon cancer cell lines SW480, HT29, and HCT15. The SP cells expressed high levels of the stem cell markers SOX2, POU5F1, LGR5, and ALDH1A1 and showed resistance to chemotherapeutic agents such as irinotecan or etoposide.To evaluate the susceptibility of SP cells to CTLs, we used CTL clone 41, which is specific for the CEP55-derived antigenic peptide Cep55/c10orf3_193 (10) (VYVKGLLAKI). The SP cells expressed HLA class I and CEP55 at the same level as the main population cells. The SP cells were susceptible to CTL clone 41 at the same level as main population cells. Furthermore, adoptive transfer of CTL clone 41 inhibited tumor growth of SW480 SP cells in vivo. These observations suggest that Cep55/c10orf3_193(10) peptide-based cancer vaccine therapy or adoptive cell transfer of the CTL clone is a possible approach for targeting chemotherapy-resistant colon CSCs/TICs.

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Available from: Hiroko Asanuma,
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    • "Recently, CSCs have been isolated from various types of malignancies, including pancreatic cancer [114–118]. According to the manner of expression in CSCs, TAAs can be classified into two categories: (i) CSC-specific antigens, such as SOX2 [119] and ALDH1A1 [120] and (ii) shared antigens, such as CEP55 [121], MUC1 [122], or WT1 [123, 124] between CSCs and more differentiated subpopulations. Several methods to isolate CSC have been reported, including cell surface markers such as CD44, CD24, CD133, or epithelial-specific antigen (ESA) and side population (SP) cells using Hoechst 33342 dye [115, 119, 120]. "
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