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9V
2 T Cell Response to Colon Carcinoma Cells1
* Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 601, Nantes, France;
Faculté des Sciences et des Techniques, Nantes, France;
Centre René Gauducheau, Nantes, France;
INSERM, Unité 539, and Laboratoire d’Anatomopathologie, Hôpital Laënnec, St. Herblain, France
During analysis of CD8 T cells derived from ascites of a colon cancer patient, we isolated a V
9V
2 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-
and IFN- 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 V9V2 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 V9V2 T cells of various origins, and V9V2 lymphocytes were present in the majority of colon tumor samples studied. Together, these results suggest that V9V2 T cells contribute to the natural immune surveillance against colon cancers. Therefore, this study provides a strong rationale for the use of V9V2 T cell agonists in immunotherapies targeting colon tumors.
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