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Molecular mechanisms used by tumors to escape immune recognition: immunogenetherapy and the cell biology of major
N P Restifo1, Y Kawakami, F Marincola
1Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Abstract:
In this article, we explore the hypothesis that tumor cells can escape recognition by CD8+ T cells via deficiencies in antigen processing and presentation. Aspects of the molecular and cellular biology of major histocompatibility complex class I are reviewed. Evidence for histology-specific molecular mechanisms in the antigen-processing and -presentation deficiencies observed in some human and murine tumors is presented. Mechanisms identified include down-regulation of antigen processing, loss of functional beta 2-microglobulin, and deletion of specific alpha-chain alleles. Finally, we discuss studies using an antigen-presentation-deficient mouse tumor as a model for the immunogenetherapy of an antigen-presentation deficiency.