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: 4.6). 04/2011; 178(4):1805-13. DOI: 10.1016/j.ajpath.2011.01.004
Source: PubMed

ABSTRACT 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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    ABSTRACT: Objective: To gain insight into the mechanism by which sex-determining region of Y chromosome (SRY)-related high-mobility-group box 2 (SOX2) involved in carcinogenesis and cancer stem cells (CSCs). Data Sources: The data used in this review were mainly published in English from 2000 to present obtained from PubMed. The search terms were "SOX2," "cancer," "tumor" or "CSCs." Study Selection: Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed. Results: SOX2, a transcription factor that is the key in maintaining pluripotent properties of stem cells, is a member of SRY-related high-mobility group domain proteins. SOX2 participates in many biological processes, such as modulation of cell proliferation, regulation of cell death signaling, cell apoptosis, and most importantly, tumor formation and development. Although SOX2 has been implicated in the biology of various tumors and CSCs, the findings are highly controversial, and information regarding the underlying mechanism remains limited. Moreover, the mechanism by which SOX2 involved in carcinogenesis and tumor progression is rather unclear yet. Conclusions: Here, we review the important biological functions of SOX2 in different tumors and CSCs, and the function of SOX2 signaling in the pathobiology of neoplasia, such as Wnt/β-catenin signaling pathway, Hippo signaling pathway, Survivin signaling pathway, PI3K/Akt signaling pathway, and so on. Targeting towards SOX2 may be an effective therapeutic strategy for cancer therapy.
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    ABSTRACT: Cancer stem cells (CSCs) represent a distinctive population of tumour cells that control tumour initiation, progression, and maintenance. Their influence is great enough to risk the statement that successful therapeutic strategy must target CSCs in order to eradicate the disease. Because cancer stem cells are highly resistant to chemo- and radiotherapy, new tools to fight against cancer have to be developed. Expression of antigens such as ALDH, CD44, EpCAM, or CD133, which distinguish CSCs from normal cells, together with CSC immunogenicity and relatively low toxicity of immunotherapies, makes immune targeting of CSCs a promising approach for cancer treatment. This review will present immunotherapeutic approaches using dendritic cells, T cells, pluripotent stem cells, and monoclonal antibodies to target and eliminate CSCs.

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May 27, 2014