Gap Junction Communication between Autologous Endothelial and Tumor Cells Induce Cross-Recognition and Elimination by Specific CTL

被引:26
作者
Benlalam, Houssem [1 ]
Jalil, Abdelali [1 ]
Hasmim, Meriem [1 ]
Pang, Baoxu [3 ]
Tamouza, Ryad [4 ]
Mitterrand, Michele [5 ]
Godet, Yann [6 ]
Lamerant, Nathalie [5 ]
Robert, Carofine [2 ]
Avril, Marie-Francoise [7 ]
Neefjes, Jacques [3 ]
Tursz, Thomas [2 ]
Mami-Chouaib, Fathia [1 ]
Kieda, Claudine [5 ]
Chouaib, Salem [1 ]
机构
[1] Inst Gustave Roussy, INSERM, U753, Inst Fed Rech 54, F-94805 Villejuif, France
[2] Inst Gustave Roussy, Dept Med, F-94805 Villejuif, France
[3] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands
[4] Hop St Louis, INSERM, Dept Immunol & Histocompatibilite, U662, Paris, France
[5] CNRS, Ctr Biophys Mol, Unite Propre Rech 4301, Orleans, France
[6] INSERM, U601, Dept Rech Cancerol, Nantes, France
[7] Univ Paris 05, Hop Cochin, AP HP, Serv Dermatol, Paris, France
关键词
CD8(+) T-CELLS; MHC CLASS-I; ANTIGEN PRESENTATION; ORGANOTYPIC CULTURE; DENDRITIC CELLS; MELANOMA-CELLS; LYMPHOCYTES; IMMUNOTHERAPY; DEGRADATION; METASTASIS;
D O I
10.4049/jimmunol.0800815
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cellular interactions in the tumor stroma play a major role in cancer progression but can also induce tumor rejection. To explore the role of endothelial cells in these interactions, we used an in vitro three-dimensional collagen matrix model containing a cytotoxic T lymphocyte CTL clone (M4.48), autologous tumor cells (M4T), and an endothelial cell (M4E) line that are A derived from the same tumor. We demonstrate in this study that specific killing of the endothelial cells by the CTL clone required the autologous tumor cells and involved Ag cross-presentation. The formation of gap junctions between endothelial and tumor cells is required for antigenic peptide transfer to endothelial cells that are then recognized and eliminated by CTL. Our results indicate that gap junctions facilitate an effective CTL-mediated destruction of endothelial cells from the tumor microenvironment that may contribute to the control of tumor progression. The Journal of Immunology, 2009, 182: 2654-2664.
引用
收藏
页码:2654 / 2664
页数:11
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