The impact of the immune system on tumour growth in humans is poorly understood. Several studies have, however, identified T cells, in particular CD8+ cytotoxic T lymphocytes (CTLs), that recognize antigenic peptides expressed on autologous tumour cells. 1, 2 These tumour antigens include tumour-specific antigens that arise through mutations in normal genes; shared tumour antigens such as cancer–testis antigens; differentiation antigens; and other self-antigens that may be over-expressed in malignant cells. In some cases, where malignancies arise as a result of virus infection, tumour cells may also express viral antigens. Although antigens of each category have been found to act as targets for T-cell responses in human patients, the ability of these T cells to promote tumour rejection remains unproven. 3

Experimental evidence obtained using murine models indicates that either CD4+ or CD8+ T-cell responses to certain tumour-associated self-antigens can indeed result in tumour rejection. 4–7 Melanocyte differentiation antigens are the best-characterized self-antigens that act as targets for tumour (melanoma) rejection. 8 Vigorous immune responses to melanocyte antigens have been shown to result, not only in tumour regression, but also in the development of autoimmune vitiligo. Vitiligo is a disease characterized by skin depigmentation following the destruction of non-malignant melanocytes, often by T cells. 9 Overall, these findings indicate that the same effector T cells can be involved in both autoimmunity and tumour immunity. Thus, mechanisms of peripheral tolerance, which inhibit the activation of autoreactive T cells, also impinge upon the induction of T-cell responses to tumour-associated self-antigens. Several mechanisms account for the lack of reactivity of T cells specific for self-antigens. Many self-reactive T cells are deleted by mechanisms of negative selection in the thymus. 10, 11 Subsequently, some T cells that escape this process die following encounter with antigen in the periphery, whilst others survive but become functionally