Broad tumor-associated expression and recognition by tumor-derived γδ T cells of MICA and MICB

Human MHC class I-related molecules, MICA and MICE, are stress-induced antigens that are recognized by a subset of gamma delta T cells expressing the variable region V(delta)1, This functional association has been found to be limited to intestinal epithelium, where these T cells are prevalent and where MICA and, presumably, MICE are mainly expressed. However, increased frequencies of V(delta)1 gamma delta T cells have been observed in various epithelial tumors; moreover, MICA/B are expressed on diverse cultured epithelial tumor cells. With freshly isolated tumor specimens, expression of MICA/B was documented in many, but not all, carcinomas of the lung, breast, kidney, ovary, prostate, and colon. In tumors that were positive for MICA/B, the frequencies of V(delta)1 gamma delta T cells were significantly higher than in those that were negative. V(delta)1 gamma delta T cell lines and clones derived from different tumors recognized MICA/B on autologous and heterologous tumor cells, In accord with previous evidence, no constraints were observed in these interactions, such as those imposed by specific peptide ligands. Thus, MICA/B are tumor-associated antigens that can be recognized, in an apparently unconditional manner, by a subset of tumor-infiltrating gamma delta T cells. These results raise the possibility that an induced expression of MICA/B, by conditions that may be related to tumor homeostasis and growth, could play a role in immune responses against tumors.