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Novel insights into the molecular mechanisms of HLA class I abnormalities

  • Focussed Research Review
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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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Abbreviations

APC:

Antigen-presenting cells

APM:

Antigen-processing machinery

β2-m:

β2-microglobuline

CTL:

Cytotoxic T lymphocytes

DC:

Dendritic cells

EGF:

Epidermal growth factor

ER:

Endoplasmic reticulum

HC:

Heavy chains

IFN:

Interferon

JAK:

Janus kinase

luc:

Luciferase

MDSC:

Myeloid-derived suppressor cells

RCC:

Renal cell carcinoma

STAT:

Signal transducers and activators of transcription

TA:

Tumor antigen

TAP:

Transporter associated with antigen processing

TCR:

T cell receptor

TFBS:

Transcription factor binding sites

TNF:

Tumor necrosis factor

Treg:

Regulatory T cells

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Acknowledgments

We would like to thank Sylvi Magdeburg and Nicole Ott for excellent secretarial help. This work was supported by grants from the DFG Se581-11-1/11-2 and DFG Se581-9-1/-2.

Conflict of interest

The authors declare that they have no conflict of interest.

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  1. Institute of Medical Immunology, Martin-Luther-University Halle-Wittenberg, Magdeburger Str. 2, 06112, Halle (Saale), Germany

    Barbara Seliger

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Correspondence to Barbara Seliger.

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This paper is a Focussed Research Review based on a presentation given at the Second International Conference on Cancer Immunotherapy and Immunomonitoring (CITIM 2011), held in Budapest, Hungary, 2nd–5th May 2011. It is part of a CII series of Focussed Research Reviews and meeting report.

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Seliger, B. Novel insights into the molecular mechanisms of HLA class I abnormalities. Cancer Immunol Immunother 61, 249–254 (2012). https://doi.org/10.1007/s00262-011-1153-9

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