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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 12; pp. 6879 - 6884
• Main Authors: Groh, Veronika, Rhinehart, Rebecca, Secrist, Heather, Bauer, Stefan, Grabstein, Kenneth H., Spies, Thomas
• Format: Journal Article
• Language: English
• Published: National Acad Sciences 08-06-1999; The National Academy of Sciences
• Subjects: Biological Sciences
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.12.6879

Human MHC class I-related molecules, MICA and MICB, are stress-induced antigens that are recognized by a subset of γδ T cells expressing the variable region V δ 1. This functional association has been found to be limited to intestinal epithelium, where these T cells are prevalent and where MICA and, presumably, MICB are mainly expressed. However, increased frequencies of V δ 1 γδ 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 δ 1 γδ T cells were significantly higher than in those that were negative. V δ 1 γδ 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 γδ 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.