Vγ9Vδ2 T cell response to colon carcinoma cells

During analysis of CD8 T cells derived from ascites of a colon cancer patient, we isolated a V gamma 9V delta 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-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 V gamma 9V delta 2 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 V gamma 9V delta 2 T cells of various origins, and V gamma 9V delta 2 lymphocytes were present in the majority of colon tumor samples studied. Together, these results suggest that V gamma 9V delta 2 T cells contribute to the natural immune surveillance against colon cancers. Therefore, this study provides a strong rationale for the use of V gamma 9V delta 2 T cell agonists in immunotherapies targeting colon tumors.