The effect of alloferon on the enhancement of NK cell cytotoxicity against cancer via the up-regulation of perforin/granzyme B secretion

被引：40

作者：

Bae, Seyeon ^{[1
]}

Oh, Keunhee ^{[1
,2
]}

Kim, Hyemin ^{[1
]}

Kim, Yejin ^{[1
]}

Kim, Hang-Rae ^{[1
]}

Hwang, Young-il ^{[1
]}

Lee, Dong-Sup ^{[1
,2
]}

Kang, Jae Seung ^{[1
,3
]}

Lee, Wang Jae ^{[1
]}

机构：

[1] Seoul Natl Univ, Coll Med, Dept Anat, Seoul 110799, South Korea

[2] Seoul Natl Univ, Coll Med, Transplantat Res Inst, Seoul 110799, South Korea

[3] Seoul Natl Univ, Med Res Ctr, Inst Complementary & Integrat Med, Seoul 110799, South Korea

来源：

IMMUNOBIOLOGY | 2013年 / 218卷 / 08期

关键词：

Alloferon; Anti-tumor; NK cell; Cytokine; Granule exocytosis; Granzyme B; NATURAL-KILLER-CELLS; MHC CLASS-I; NUDE-MICE; T-CELLS; RECEPTORS; PATHWAYS; RECOGNITION; COMBINATION; ACTIVATION; EXPRESSION;

D O I：

10.1016/j.imbio.2012.12.002

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Alloferon is a novel immunomodulatory peptide originally isolated from infected insects. It has antiviral and anti-tumor effects via the activation of NK cells. However, specific mechanisms leading to NK cell activation and anti-tumor responses yet to be clarified. In this study, we demonstrate that alloferon increases killing activity of NK cells to cancer cells via the up-regulation of the expression of NK-activating receptors, 2B4. In addition, the production of IFN-gamma and TNF-alpha and granule exocytosis from NK cells against cancer cell were increased by alloferon. Lastly, the anti-tumor effect of alloferon was confirmed in vivo to demonstrate effective retardation of tumor growth in the human-to-mouse xenograft model. All taken together, these results suggest that alloferon has anti-tumor effects through up-regulation of NK-activating receptor 2B4 and the enhancement of granule exocytosis from NK cells. (C) 2013 Elsevier GmbH. All rights reserved.

引用

页码：1026 / 1033

页数：8

共 36 条

[1] CD107a as a functional marker for the identification of natural killer cell activity [J].

Alter, G ;

Malenfant, JM ;

Altfeld, M .

JOURNAL OF IMMUNOLOGICAL METHODS, 2004, 294 (1-2) :15-22

[2] Antiviral and antitumor peptides from insects [J].

Chernysh, S ;

Kim, SI ;

Bekker, G ;

Pleskach, VA ;

Filatova, NA ;

Anikin, VB ;

Platonov, VG ;

Bulet, P .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) :12628-12632

[3] Anti-tumor activity of immunomodulatory peptide alloferon-1 in mouse tumor transplantation model [J].

Chernysh, Sergey ;

Irina, Kozuharova ;

Irina, Artsibasheva .

INTERNATIONAL IMMUNOPHARMACOLOGY, 2012, 12 (01) :312-314

[4] 2B4 (CD244)-mediated activation of cytotoxicity and IFN-γ release in human NK cells involves distinct pathways [J].

Chuang, SS ;

Kumaresan, PR ;

Mathew, PA .

JOURNAL OF IMMUNOLOGY, 2001, 167 (11) :6210-6216

[5]

Fehniger TA, 1999, J IMMUNOL, V162, P4511

[6] Attenuation of the glucocorticoid response during Ad5IL-12 adenovirus vector treatment enhances natural killer cell-mediated killing of MHC class I-negative LNCaP prostate tumors [J].

Gabaglia, Claudia Raja ;

de Durana, Yaiza Diaz ;

Graham, Frank L. ;

Gauldie, Jack ;

Sercarz, Eli E. ;

Braciak, Todd A. .

CANCER RESEARCH, 2007, 67 (05) :2290-2297

[7]

GARNIWAGNER BA, 1993, J IMMUNOL, V151, P60

[8] Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells [J].

Hsu, FJ ;

Benike, C ;

Fagnoni, F ;

Liles, TM ;

Czerwinski, D ;

Taidi, B ;

Engleman, EG ;

Levy, R .

NATURE MEDICINE, 1996, 2 (01) :52-58

[9] Enhanced cytotoxicity of allogeneic NK cells with killer immunoglobulin-like receptor ligand incompatibility against melanoma and renal cell carcinoma cells [J].

Igarashi, T ;

Wynberg, J ;

Srinivasan, R ;

Becknel, B ;

McCoy, JP ;

Takahashi, Y ;

Suffredini, DA ;

Linehan, WM ;

Caligiuri, MA ;

Childs, RW .

BLOOD, 2004, 104 (01) :170-177

[10] NOD/SCID/γcnull mouse:: an excellent recipient mouse model for engraftment of human cells [J].

Ito, M ;

Hiramatsu, H ;

Kobayashi, K ;

Suzue, K ;

Kawahata, M ;

Hioki, K ;

Ueyama, Y ;

Koyanagi, Y ;

Sugamura, K ;

Tsuji, K ;

Heike, T ;

Nakahata, T .

BLOOD, 2002, 100 (09) :3175-3182

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