Molecular mechanisms used by tumors to escape immune recognition: immunogenetherapy and the cell biology of major histocompatibility complex class I.
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.
Restifo
N P
NP
Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Kawakami
Y
Y
Marincola
F
F
Shamamian
P
P
Taggarse
A
A
Esquivel
F
F
Rosenberg
S A
SA
D000818:Animals; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm; D003131:Combined Modality Therapy; D015316:Genetic Therapy; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000235:genetics; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma