V gamma 9V delta 2 T cell response to colon carcinoma cells.
During analysis of CD8 T cells derived from ascites of a colon cancer patient, we isolated a Vgamma9Vdelta2 T cell clone showing strong reactivity against autologous tumor cell lines. This clone killed a large fraction of allogeneic colon carcinoma and melanoma cell lines, but did not affect a normal colon cell line, colon fibroblasts, or melanocytes. Tumor cell recognition was TCR and NKG2D dependent and induced TNF-alpha and IFN-gamma secretion by the clone; accordingly, tumor targets expressed several NKG2D ligands, such as MHC class I chain-related gene A and UL16-binding protein molecules. Colon tumor recognition by Vgamma9Vdelta2 T cells was highly dependent on isopentenyl pyrophosphate production and ICAM-1 expression by target cells. Finally, similar reactivity patterns against colon carcinoma cell lines were observed using polyclonal Vgamma9Vdelta2 T cells of various origins, and Vgamma9Vdelta2 lymphocytes were present in the majority of colon tumor samples studied. Together, these results suggest that Vgamma9Vdelta2 T cells contribute to the natural immune surveillance against colon cancers. Therefore, this study provides a strong rationale for the use of Vgamma9Vdelta2 T cell agonists in immunotherapies targeting colon tumors.
Corvaisier
Murielle
M
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 601, Nantes, France.
Moreau-Aubry
Agnès
A
Diez
Elisabeth
E
Bennouna
Jaafar
J
Mosnier
Jean-Francois
JF
Scotet
Emmanuel
E
Bonneville
Marc
M
Jotereau
Francine
F
D000941:Antigens / Q000276:immunology; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002999:Clone Cells; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D055607:Receptors, Natural Killer Cell; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000941:Antigens; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D018799:Intercellular Adhesion Molecule-1