Gap junction communication between autologous endothelial and tumor cells induce cross-recognition and elimination by specific CTL.
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 all 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.
Benlalam
Houssem
H
Institut National de la Santé et de la Recherche Médicale Unite 753, Institut Fédératif de Recherche 54, Villejuif, France.
Jalil
Abdelali
A
Hasmim
Meriem
M
Pang
Baoxu
B
Tamouza
Ryad
R
Mitterrand
Michèle
M
Godet
Yann
Y
Lamerant
Nathalie
N
Robert
Caroline
C
Avril
Marie-Françoise
MF
Neefjes
Jacques
J
Tursz
Thomas
T
Mami-Chouaib
Fathia
F
Kieda
Claudine
C
Chouaib
Salem
S
D000951:Antigens, Neoplasm / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D045744:Cell Line, Tumor; D002999:Clone Cells; D018920:Coculture Techniques; D045142:Cross-Priming / Q000276:immunology*; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D017629:Gap Junctions / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor