title: The dual-functional capability of cytokine-induced killer cells and application in tumor immunology.
abstract: Cytokine-induced killer (CIK) cells represent a heterogeneous cell population, including a large majority of CD3+CD56+ cells, a relatively minor fractions of typical T cells (CD3+CD56-), and natural killer (NK) cells (CD3-CD56+). In order to elucidate the tumor killing mechanism of these three subpopulations of CIK cells, this review summarized the concordances and differences among CD3+CD56+ CIK cells, CD3-CD56+ NK cells and CD3+CD56- T cells to the following aspects: the effects of cell surface molecules, mechanisms of tumor killing, and clinical applications of these cells in immunotherapy. NK cells can be classified into CD56brightCD16- NK cells, which produce cytokines in response to monokine co-stimulation, and the CD56dimCD16+ NK cells, which contribute to lysing susceptible target. Also, the immunity of NK cells is mainly regulated by several immune-receptors, such as ACR, ICR, NCR and KIRs. T cells require TCR and co-stimulatory molecules for initiation of T cell activation. The CD3+CD56+ CIK cells co-express with T-cell marker CD3 and NK cell marker CD56 to appear the most potent cytotoxicity and high impact on adoptive cellular immunotherapy. These CIK subpopulations share some similar tumor killing mechanisms. LFA-1 not only mediates the binding of NK cells to target cells through its ligand ICAM-1 to localize actin accumulation but also acts as a co-stimulatory receptor on NK cells. LFA-1 also functions as co-stimulatory receptor for T cells to transmit intracellular signals from the TCR to LFA-1. Furthermore, cytotoxic effect of CD3+CD56+ CIK cells is blocked by antibodies directly against LFA-1 and its counter receptor, ICAM-1. Clinically, antibody-dependent cell-mediated cytotoxicity (ADCC) is shown in both NK cells and T cells for tumor killing while dendritic cells are another main regulator for the activation of three subpopulations. In summary, CD3+CD56+ CIK cells have dual-functional capability as T-cell subsets which acquire NK cells function and reserve TCR-mediated specific cytotoxicity. Meanwhile, CIK cells play important roles in tumor immunology. It paves the way to more effective immunotherapies for various tumors.
authors.affiliation: Department of mammary gland, LiaoNing Tumor Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning 110042, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of mammary gland, LiaoNing Tumor Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning 110042, China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Dalian Medical University Graduate School, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of mammary gland, LiaoNing Tumor Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning 110042, China.
authors.forename: Xin-feng
authors.initials: XF
authors.lastname: Zhang
authors.affiliation: Department of mammary gland, LiaoNing Tumor Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning 110042, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of mammary gland, LiaoNing Tumor Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning 110042, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Long
authors.affiliation: Department of mammary gland, LiaoNing Tumor Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning 110042, China.
authors.forename: Zhuang-kai
authors.initials: ZK
authors.lastname: Liu
authors.affiliation: Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang, Liaoning 110001, China. Electronic address: wangeh6@163.com.
authors.forename: En-hua
authors.initials: EH
authors.lastname: Wang
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D055612:Cytokine-Induced Killer Cells / Q000276:immunology* / Q000637:transplantation; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D020239:Receptor Cross-Talk; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1
keywords: CD3+CD56+ cells; Cytokine-induced killer (CIK) cells; Natural killer (NK) cells; T cells; Tumor immunology