TAP expression provides a general method for improving the recognition
of malignant cells in vivo
Judy Alimonti2, Qian-Jin Zhang2, Reinhard Gabathuler1, Gregor Reid1, Susan S. Chen1
& Wilfred A. Jefferies1
1
The Biotechnology Laboratory, Biomedical Research Centre,
and the Departments of Medical Genetics, Microbiology and Immunology, and
Zoology, 2222 Health Sciences Mall, University of British Columbia,
Vancouver, BC V6T 1Z3, Canada.
Correspondence should be addressed to Wilfred A. Jefferies wilf@brc.ubc.ca
A major class of tumors lack expression of the transporters associated
with antigen processing (TAP). These proteins are essential for delivery of
antigenic peptides into the lumen of the endoplasmic reticulum (ER) and subsequent
assembly with nascent major histocompatibility complex (MHC) class I, which
results in cell surface presentation of the trimeric complex to cytolytic
T lymphocytes. Cytolytic T lymphocytes are major effector cells in immunosurveillance
against tumors. Here we have tested the hypothesis that TAP downregulation
in tumors allows immunosubversion of this effector mechanism, by establishing
a model system to examine the role of TAP in vivo in restoring antigen presentation,
immune recognition, and effects on malignancy of the TAP-deficient small-cell
lung carcinoma, CMT.64. To test the potential of providing exogenous TAP in
cancer therapies, we constructed a vaccinia virus (VV) containing the TAP1
gene and examined whether VV-TAP1 could reduce tumors in mice. The results
demonstrate that TAP should be considered for inclusion in cancer therapies,
as it is likely to provide a general method for increasing immune responses
against tumors regardless of the antigenic complement of the tumor or the
MHC haplotypes of the host.
