Because tumor-specific cytotoxic T lymphocytes (CTL) recognize tumor antigen associated with MHC class I molecules expressed on the tumor surface, any alteration in the tumor antigen processing and presentation will greatly affect CTL immunity. In fact, downregulation or complete loss of MHC I molecules have been demonstrated in a wide array of tumors, particularly prostate, colon, lung, and breast cancers (5-12). Disruption or downregulation of antigen processing components, such as TAP (transporters associated with antigen processing) and LMP (components of the proteasome complex) genes have also been observed in several tumor types, including breast, prostate, and renal cancers (13-15). Another tactic tumors exploit is downregulation or alteration of tumor antigens. Several independent research groups described the loss of melanoma-associated antigen either during treatment by adoptive transfer of ex vivo expanded antigen-specific CTL (16) or during immune therapy by tumor vaccinations (12,17,18).
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