MHC class I down-regulation: tumour escape from immune surveillance? (Review)

  • Authors: Jan Bubeník
  • View Affiliations

  • Published online on: Sunday, August 1, 2004
  • Pages: 487-491
  • DOI: 10.3892/ijo.25.2.487

Abstract

Malignant conversion and subsequent in vivo selection can give rise to the cell populations that show stable expression of an immune escape phenotype, MHC class I deficient neoplasms. Deficiencies associated with the MHC class I down-regulation are either irreversible, such as β2 microglobulin and class I heavy chain gene disabling mutations, or reversible. The reversible MHC class I deficiencies involve all levels of the MHC class I-restricted antigen presentation machinery. They can be repaired, at least partially and in vitro, by cytokines (IFNγ, TNFα) or by DNA demethylation/histone hyperacetylation procedures. The reduced levels of MHC class I antigens result in decreased sensitivity to MHC class I-restricted, cytotoxic T lymphocyte-mediated lysis, the major component of the tumour rejection reaction. MHC class I down-regulation helps tumour cells evade the classical T cell-dependent immune responses but simultaneously imposes another, the NK cell-mediated, surveillance stimulated by the ‘missing self’ signals. The innate and adaptive antitumour immunity may be under some conditions interconnected: primary activation of the MHC class I-unrestricted surveillance mechanisms may lead to the production of IFNγ by the activated NK/γδ T cells; the in situ produced IFNγ may then up-regulate the MHC class I molecule expression on the tumour cell surface and in this way it may stimulate the more efficient, MHC class I-restricted, adaptive immunity. If we accept that the MHC class I down-regulation can, under some conditions, indeed be a mechanism of the tumour escape from the immune defence, the problem arises how to cope efficiently with this escape. Either therapeutic procedures aiming at up-regulation of MHC class I expression, or enhancement of MHC class I-unrestricted (CD4+, NK, NKT, γδ T) tumour defence effector mechanisms by dendritic cell-based therapeutic vaccines, by cytokines (IL-2, IL-12, IFNγ, GM-CSF), or by the cytokine gene-based, genetically modified tumour vaccines should be considered.
Journal Cover

August 2004
Volume 25 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
& Bubeník, J. (2004). MHC class I down-regulation: tumour escape from immune surveillance? (Review). International Journal of Oncology, 25(2), 487-491.
MLA
and Jan Bubeník. "MHC class I down-regulation: tumour escape from immune surveillance? (Review)." International Journal of Oncology International Journal of Oncology 25.2 (2004): 487-491.
Chicago
and Jan Bubeník. "MHC class I down-regulation: tumour escape from immune surveillance? (Review)." International Journal of Oncology International Journal of Oncology 25 no. 2 (2004): 487-491.