title: Autologous CTL response against cancer stem-like cells/cancer-initiating cells of bone malignant fibrous histiocytoma.
abstract: Malignant fibrous histiocytoma (MFH) of the bone is an aggressive tumor with high rates of local recurrence and metastasis. The development of novel therapeutic approaches is critical to improve the prognosis of patients with MFH. We reported previously that the side population (SP) cells of the MFH2003 bone MFH cell line have the characteristics of cancer stem-like cells (CSC)/cancer-initiating cells. In the present study, to establish immunotherapy targeting CSC, we analyzed cell surface immune molecules on SP cells of the MHF2003 cell line, as well as autologous CTL responses against these SP cells in the tumor microenvironment and peripheral circulating lymphocytes, using autologous tumor-infiltrating lymphocytes and autologous CTL clones derived from peripheral blood, respectively. We found that the SP cells expressed human leukocyte antigen (HLA) Class I molecules on the cell surface. The autologous tumor-infiltrating lymphocyte line TIL2003 recognized both the SP and main population cells of the MFH2003 cell line. Next, we induced the CTL clone Tc4C-6 by mixed lymphocyte tumor cell culture using autologous peripheral blood mononuclear cells and freshly isolated SP cells, followed by a limiting dilution procedure. The Tc4C-6 clone showed specific cytotoxicity against the SP cells. Moreover, the cytotoxicity against SP cells was blocked by the anti-HLA Class I antibody W6/32. In conclusion, the findings of the present study support the idea that CSC of bone MFH are recognized by autologous CTL in the tumor microenvironment and peripheral circulating lymphocytes. Thus, CTL-based immunotherapy could target CSC of bone sarcoma to help prevent tumor recurrence.
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.forename: Makoto
authors.initials: M
authors.lastname: Emori
authors.forename: Masaki
authors.initials: M
authors.lastname: Murase
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawaguchi
authors.forename: Takuro
authors.initials: T
authors.lastname: Wada
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D001859:Bone Neoplasms / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D051677:Histiocytoma, Malignant Fibrous / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D014411:Neoplastic Stem Cells / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*