Impediments to successful immunotherapy.

Over the last decade, there has been a considerable increase in understanding of immune responses against cancers, the antigenic structures on tumor cells recognised by the immune system, and the development of more effective vaccines. There is, however, very limited understanding of why the immune system most often fails to control tumor growth and progression. In some patients, it is difficult to demonstrate immune responses to their tumors, and it may be assumed that this reflects poor recognition of tumor antigens, induction of anergy in lymphocytes, or suppression of immune responses by tumor-derived factors. In other patients, tumor progression appears to occur despite the presence of antibody or cell-mediated responses. This may indicate selection of tumor cells that have lost tumor antigens or HLA antigens by immune responses against the tumor. Tumor cells may also become resistant to mediators of apoptosis, such as Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand used by lymphocytes to kill tumor cells. It is suggested that development of effective immunotherapy will need to include strategies that take into account these limitations of immune responses and classification of tumors according to the treatment approach most likely to succeed.