umor-specific immune responses have been well demonstrated experimentally in animals and, more recently, tumor-specific and tumor-associated antigens (TAAs) have been identified for several cancers 1Ð3 . Although the promise of tumor immunology has yet to be fulfilled, it is noteworthy that several of the likely mechanisms by which tumors escape immune surveillance have only been unraveled at a fundamental molecular level in recent years. Future approaches to the immunotherapy of tumors will need to be reconciled with such mechanisms of immune escape and must exploit counterstrategies.
Tumors have evolved multiple mechanisms for evading the immune system. These range from a passive failure to express costimulatory and major histocompatibility complex (MHC) molecules 4,5 to active strategies such as the production of immunosuppressive cytokines and other factors 6,7 . Passive and active processes are also involved in the most recently discovered mechanism by which tumors may evade the immune system Ð the Fas counterattack.
Tumor immune privilege (resistance and counterattack)
The Fas receptor (Fas, APO-1/CD95) and its ligand (FasL, CD95L) are transmembrane proteins of the tumor necrosis factor (TNF) family of receptors and ligands. Engagement of Fas by FasL triggers a cascade of subcellular events that result in programmed cell death (apoptosis). Fas-mediated apoptosis has a fundamental role in immune homeostasis 8 . MJAlthough FasL was initially thought to be expressed only in cells of the lymphoid/myeloid series including T cells, natural killer (NK) cells, B cells and phagocytes, it has recently been shown to be expressed by non-lymphoid cells, where it contributes to immune privilege by inducing apoptosis in infiltrating proinflammatory immunocytes 9,10 . This helps to preclude inflammatory reactions from organs where inflammatory damage could be hazardous to the organismÕs survival. The concept of immune privilege is not new but the mechanism by which the privileged status of tissues such as the eye, the brain and reproductive organs is maintained has, until recently, been unclear and often considered