TAP expression provides a general method for improving the recognition of malignant cells in vivo

A major class of tumors lack expression of the transporters associated with antigen processing (TAP). These proteins are essential for delivery of ant igenic peptides into the lumen of the endoplasmic reticulum (ER) and subseq uent assembly with nascent major histocompatibility complex (MHC) class I, which results in cell surface presentation of the trimeric complex to cytol ytic T lymphocytes. Cytolytic T lymphocytes are major effector cells in imm unosurveillance against tumors. Here we have tested the hypothesis that TAP downregulation in tumors allows immunosubversion of this effector mechanis m, by establishing a model system to examine the role of TAP in vivo in res toring antigen presentation, immune recognition, and effects on malignancy of the TAP-deficient small-cell lung carcinoma, CMT.64. To test the potenti al of providing exogenous TAP in cancer therapies, we constructed a vaccini a virus (VV) containing the TAP1 gene and examined whether W-TAP1 could red uce tumors in mice. The results demonstrate that TAP should be considered f or inclusion in cancer therapies, as it is likely to provide a general meth od for increasing immune responses against tumors regardless of the antigen ic complement of the tumor or the MHC haplotypes of the host.