title: Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells.
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.
authors: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Satoko
authors: S
authors: Inoda
authors: Yoshihiko
authors: Y
authors: Hirohashi
authors: Toshihiko
authors: T
authors: Torigoe
authors: Rena
authors: R
authors: Morita
authors: Akari
authors: A
authors: Takahashi
authors: Hiroko
authors: H
authors: Asanuma
authors: Munehide
authors: M
authors: Nakatsugawa
authors: Satoshi
authors: S
authors: Nishizawa
authors: Yasuaki
authors: Y
authors: Tamura
authors: Tetsuhiro
authors: T
authors: Tsuruma
authors: Takeshi
authors: T
authors: Terui
authors: Toru
authors: T
authors: Kondo
authors: Kunihiko
authors: K
authors: Ishitani
authors: Tadashi
authors: T
authors: Hasegawa
authors: Koichi
authors: K
authors: Hirata
authors: Noriyuki
authors: N
authors: Sato
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000276:immunology*; D010455:Peptides / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*
chemical_list: D000941:Antigens; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D010455:Peptides; D005047:Etoposide; D000077146:Irinotecan; C017807:bisbenzimide ethoxide trihydrochloride; D002166:Camptothecin