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Review
. 2012 Feb;61(2):249-254.
doi: 10.1007/s00262-011-1153-9. Epub 2011 Nov 27.

Novel insights into the molecular mechanisms of HLA class I abnormalities

Barbara Seliger  1
Affiliations
Review

Novel insights into the molecular mechanisms of HLA class I abnormalities

Barbara Seliger. Cancer Immunol Immunother. 2012 Feb.

Abstract

Alterations in the MHC class I surface antigens represent one mechanism of tumor cells to escape from natural or immunotherapy-induced antitumor immune responses. In order to restore MHC class I expression, knowledge about the underlying molecular mechanisms of MHC class I defects in different tumor types is required. In most cases, abnormalities of MHC class I expression are reversible by cytokines suggesting a deregulation rather than structural abnormalities of members of the antigen-processing and presentation machinery (APM). The impaired expression of APM components could be controlled at the epigenetic, transcriptional and/or posttranscriptional level. Furthermore, a direct link between altered transcription factor binding, interferon signal transduction and MHC class I APM component expression has been shown, which might be further associated with cell cycle progression. This information will not only give novel insights into the (patho) physiology of the antigen-processing and presenting pathway, but will help in the future to design effective T cell-based immunotherapies.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Different immune escape mechanisms of tumors. Tumors exert different strategies to escape immune cell surveillance. In addition, the frequency and function of immune cells are altered by the tumor microenvironment, which also results in an impaired anti tumor immune response
Fig. 2
Fig. 2
Molecular mechanisms of MHC class I APM downregulation. The loss or downregulated expression of APM components could occur at the distinct levels of the MHC class I APM pathway and involves transcriptional, posttranscriptional and epigenetic processes resulting in a deregulated expression, whereas structural alterations like mutations, deletions and LOH are rare events
See this image and copyright information in PMC

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References

    1. Nagaraj S, Gabrilovich DI. Myeloid-derived suppressor cells in human cancer. Cancer J. 2010;16(4):348–353. doi: 10.1097/PPO.0b013e3181eb3358. - DOI - PubMed
    1. Lu T, Ramakrishnan R, Altiok S, Youn JI, Cheng P, Celis E, Pisarev V, Sherman S, Sporn MB, Gabrilovich D (2011) Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. J Clin Invest. doi:10.1172/JCI45862 - PMC - PubMed
    1. Scholz C, Tampe R. The peptide-loading complex—antigen translocation and MHC class I loading. Biol Chem. 2009;390(8):783–794. doi: 10.1515/BC.2009.069. - DOI - PubMed
    1. Ferrone S, Marincola FM. Loss of HLA class I antigens by melanoma cells: molecular mechanisms, functional significance and clinical relevance. Immunol Today. 1995;16(10):487–494. doi: 10.1016/0167-5699(95)80033-6. - DOI - PubMed
    1. Campoli M, Ferrone S. HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. Oncogene. 2008;27(45):5869–5885. doi: 10.1038/onc.2008.273. - DOI - PMC - PubMed

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