Cancer Antigens Uncovered

The potential of T cells to invade and attack tumors forms the basis for some very promising avenues of cancer immunotherapy. However, progress is often hampered by poor characterization of the antigens that killer T lymphocytes use to target tumor cells. Savage et al. (see the Perspective by Schreiber and Rowley) describe a broadly recognized antigen in a mouse model of prostate cancer. Unusually, the antigen was derived from a ubiquitous histone protein that is normally compartmentalized away from detection by the immune system. However, in the context of the tumor, the antigen was revealed to potentially reactive T cells, which suggests that the tumor environment somehow bends the rules of antigen processing and engagement by the immune system. Because features of this model are similar to those seen in human cancers, the system may also be useful in exploring tumor detection and therapeutic immune intervention. P. A. Savage, K. Vosseller, C. Kang, K. Larimore, E. Riedel, K. Wojnoonski, A. A. Jungbluth, J. P. Allison, Recognition of a ubiquitous self antigen by prostate cancer-infiltrating CD8 + T lymphocytes. Science 319 , 215-220 (2008). [Abstract][Full Text] H. Schreiber, D. A. Rowley, Quo vadis, specificity? Science 319 , 164-165 (2008). [Summary][Full Text]