MHC Class I: The Cancer Connection

Major histocompatibility complex (MHC)

By Simon Hackett

Major histocompatibility complex (MHC) molecules, also known as human leukocyte antigens (HLA) are a locus of genes located on chromosome 6 that regulate and control immune system homeostasis. As well as playing an important role in the presentation of peptides to the immune system, MHC molecules have a wide range of other roles in cancer and autoimmune diseases. Indeed, the down-regulation or total loss of expression of MHC class I contributes to the evasion of cancer cells from the host immune system by preventing the presentation of peptides to cancer-specific T cells, as well as NK cells.

In order to further characterize the relationship between MHC class I and cancer, Xiaogang et al. looked at loss of heterozygosity on chromosome 6 and correlated it with class I MHC expression in tumors. The team examined 86 sections from human esophageal squamous cell carcinomas against control esophageal tissues for the expression of MHC class I. Using Proteintech antibody 66013-1-Ig, specific for MHC class IA (see Box 1), the authors were able to show homogenous staining of MHC class I in the control specimens compared with significantly variable expression in tumor specimens. The expression of MHC class I was either down-regulated or completely absent in 23% and 34.5% of tumor sections, respectively.

This is not the first report that MHC class I is down-regulated in cancer cells as reflected by the wide-body of literature on the subject. As outlined earlier, it is thought that the down-regulation of MHC class I on tumor cells is thought to be part of an evolutionary mechanism in order to evade the immune system. Indeed, there is a strong correlation between MHC class I expression and tumor prognosis: tumors exhibiting lower levels of MHC class I reflect a less favorable prognostic outcome.

MHC molecules are split into three categories:

  • MHC class I, which are split into three further categories of A, B and C. These molecules present peptides that are broken inside the cell, transported to the cell surface and loaded on to MHC class I molecules.
  • MHC class II, which are split into six further categories of DP, DM, DOA, DQ and DR. MHC class II molecules present antigens from outside of the cell to T cells, which results in T cell activation and the production of antibodies by B cells.
  • MHC class III, which regulate the expression of the complement factors.

Therapeutic potential

The relationship between MHC and cancerous cells has been targeted therapeutically with the use of NK cells. As outlined earlier, NK cells target cell possessing non-self MHC class I. Given that MHC class I expression is often altered in cancerous tissue, there have been several clinical trials looking at the efficacy of infusing allogeneic NK cells into individuals with cancer. Although the outcomes of many of the trials have been mixed, studies have shown some efficacy in patients with melanoma.

It is therefore clear that the relationship between MHC class I expression and cancer is an important area of interest in the rapidly expanding field of cancer therapy. Proteintech offer a wide range of antibodies recognizing human, mouse and rat MHC/HLA molecules applicable to your research needs, which you can find here.

References

Arai, S et al. (2008) Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. Cytotherapy. 10, 625-32

Cho, D et al. (2011) NK cell-based immunotherapy for treating cancer: will it be promising? K. J. Haematol. 46, 3-5.

Ferris et al. (2005) Human leukocyte antigen (HLA) class I defects in head and neck cancer: molecular mechanisms and clinical significance. Immunol. Res. 33, 113-133.

Hicklin, D. J et al. (1999) HLA class I antigen downregulation in human cancers: T-cell immunotherapy revives an old story. Mol. Med. Today. 5, 178-186.

Xiaogang, Z. et al. (2011) Loss of heterozygosity at 6p21 and HLA class I expression in esophageal squamous cell carcinomas in China. Asian Pacific J. Cancer Prev. 12, 2741-2745.

Zeestraten et al. (2013) Combined analysis of HLA class I, HLA-E and HLA-G predicts prognosis in colon cancer patients. B. J. Cancer. 1-10

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Posted:
14 August, 2014

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