PMID- 21518139 OWN - NLM STAT- MEDLINE DCOM- 20110913 LR - 20110719 IS - 1349-7006 (Electronic) IS - 1347-9032 (Linking) VI - 102 IP - 8 DP - 2011 Aug TI - Autologous CTL response against cancer stem-like cells/cancer-initiating cells of bone malignant fibrous histiocytoma. PG - 1443-7 LID - 10.1111/j.1349-7006.2011.01962.x [doi] AB - 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. CI - (c) 2011 Japanese Cancer Association. FAU - Kano, Masanobu AU - Kano M AD - Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Tsukahara, Tomohide AU - Tsukahara T FAU - Emori, Makoto AU - Emori M FAU - Murase, Masaki AU - Murase M FAU - Torigoe, Toshihiko AU - Torigoe T FAU - Kawaguchi, Satoshi AU - Kawaguchi S FAU - Wada, Takuro AU - Wada T FAU - Yamashita, Toshihiko AU - Yamashita T FAU - Sato, Noriyuki AU - Sato N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110531 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 SB - IM MH - Bone Neoplasms/immunology/*therapy MH - Cell Line, Tumor MH - Cytotoxicity, Immunologic MH - Histiocytoma, Malignant Fibrous/immunology/*therapy MH - Humans MH - Immunotherapy MH - Lymphocytes, Tumor-Infiltrating/immunology MH - Neoplastic Stem Cells/*immunology MH - T-Lymphocytes, Cytotoxic/*immunology EDAT- 2011/04/27 06:00 MHDA- 2011/09/14 06:00 CRDT- 2011/04/27 06:00 PHST- 2011/04/27 06:00 [entrez] PHST- 2011/04/27 06:00 [pubmed] PHST- 2011/09/14 06:00 [medline] AID - 10.1111/j.1349-7006.2011.01962.x [doi] PST - ppublish SO - Cancer Sci. 2011 Aug;102(8):1443-7. doi: 10.1111/j.1349-7006.2011.01962.x. Epub 2011 May 31.