Exosomes and the MICA-NKG2D system in cancer

被引:142
作者
Clayton, A [1 ]
Tabi, Z [1 ]
机构
[1] Cardiff Univ, Dept Clin Oncol & Palliat Med, Wales Coll Med, Velindre Canc Ctr, Cardiff CF14 2TL, Wales
关键词
exosome; MICA; NKG2D; cancer;
D O I
10.1016/j.bcmd.2005.03.003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Exosomes are nanometer sized vesicles, secreted by a diverse range of cell types, whose biological functions rem ambiguous. Several groups have demonstrated the potential of manipulating exosomes for activating cellular immune responses. The possibility that exosomes may inhibit immunological responses, however, has not been widely addressed. We have investigated if exosomes produced by tumor cells can inhibit immunological functions, through modulating expression of the NKG2D) receptor by effector cells. Incubating tumor exosomes with fresh peripheral blood leukocytes resulted in a marked reduction in the proportion of NKG2D-positive CD3+ CD8+ Cells, and CD3- cells by 48 It. This effect was dose dependent and was shown with exosomes from different tumor cells including breast cancer and mesothelioma. Analysis of tumor exosome-phenotype revealed positive expression of several NKG2D ligands, and antibody blocking experiments revealed the importance of such ligands in driving the reduction in the proportion of NKG2D-positive effector cells. The functional importance of the decrease in NKG2D-positive cells was addressed in vitro cytotoxicity assays. For example a CD8+ T cell line pre-incubated with tumor exosomes had significant decreased capacity to kill peptide-pulsed T2 target cells. These data highlight a role for turner exosomes bearing NKG2D ligands as a mechanism contributing to cancer immune evasion. 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:206 / 213
页数:8
相关论文
共 14 条
  • [1] Malignant effusions and immunogenic tumour-derived exosomes
    Andre, F
    Schartz, NEC
    Movassagh, M
    Flament, C
    Pautier, P
    Morice, P
    Pomel, C
    Lhomme, C
    Escudier, B
    Le Chevalier, T
    Tursz, T
    Amigorena, S
    Raposo, G
    Angevin, E
    Zitvogel, L
    [J]. LANCET, 2002, 360 (9329) : 295 - 305
  • [2] Two human ULBP/RAET1 molecules with transmembrane regions are ligands for NKG2D
    Bacon, L
    Eagle, RA
    Meyer, M
    Easom, N
    Young, NT
    Trowsdale, J
    [J]. JOURNAL OF IMMUNOLOGY, 2004, 173 (02) : 1078 - 1084
  • [3] UL16 binding proteins
    Cao, W
    He, W
    [J]. IMMUNOBIOLOGY, 2004, 209 (03) : 283 - 290
  • [4] Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice
    Cerwenka, A
    Bakker, ABH
    McClanahan, T
    Wagner, J
    Wu, J
    Phillips, JH
    Lanier, LL
    [J]. IMMUNITY, 2000, 12 (06) : 721 - 727
  • [5] ULBP4 is a novel ligand for human NKG2D
    Chalupny, NJ
    Sutherland, CL
    Lawrence, WA
    Rein-Weston, A
    Cosman, D
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 305 (01) : 129 - 135
  • [6] Ovarian carcinoma expresses the NKG2D ligand letal and promotes the survival and expansion of CD28- antitumor T cells
    Conejo-Garcia, JR
    Benencia, F
    Courreges, MC
    Gimotty, PA
    Khang, E
    Buckanovich, RJ
    Frauwirth, KA
    Zhang, L
    Katsaros, D
    Thompson, CB
    Levine, B
    Coukos, G
    [J]. CANCER RESEARCH, 2004, 64 (06) : 2175 - 2182
  • [7] Cosman D, 2001, IMMUNITY, V14, P123, DOI 10.1016/S1074-7613(01)00095-4
  • [8] Ligands for the murine NKG2D receptor: expression by tumor cells and activation of NK cells and macrophages
    Diefenbach, A
    Jamieson, AM
    Liu, SD
    Shastri, N
    Raulet, DH
    [J]. NATURE IMMUNOLOGY, 2000, 1 (02) : 119 - 126
  • [9] Production and characterization of clinical grade exosomes derived from dendritic cells
    Lamparski, HG
    Metha-Damani, A
    Yao, JY
    Patel, S
    Hsu, DH
    Ruegg, C
    Le Pecq, JB
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 2002, 270 (02) : 211 - 226
  • [10] Natural killer cell receptors for major histocompatibility complex class I and related molecules in cytomegalovirus infection
    López-Botet, M
    Angulo, A
    Gumá, M
    [J]. TISSUE ANTIGENS, 2004, 63 (03): : 195 - 203