The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape - PubMed (original) (raw)

Review

The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape

Ignacio Algarra et al. Cancer Immunol Immunother. 2004 Oct.

Abstract

Tumor immune escape variants can be identified in human and experimental tumors. A variety of different strategies are used by tumor cells to avoid recognition by different immune effector mechanisms. Among these escape routes, alteration of MHC class I cell surface expression is one of the mechanisms most widely used by tumor cells. In this review we focus our attention on the T-cell immune selection of MHC class I-deficient tumor variants. Different altered MHC class I phenotypes that originate from multiple molecular mechanisms can be identified in human tumors. MHC-deficient tumor clones can escape T-cell immune responses, but are in theory more susceptible to NK-cell-mediated lysis. In this context, we also review the controversial issue of the aberrant expression of nonclassical HLA class I molecules, particularly HLA-G, in tumors. This expression may be relevant in tumor cells that have lost the capacity to interact with NK inhibitory receptors-namely, those tumor cells with no HLA-B or HLA-C expression. Most published studies have not analyzed these possibilities and do not provide information about the complete HLA-A, HLA-B, or HLA-C molecule profiles of the tumors studied. In contrast, HLA-E has been reported to be expressed in some tumor cell lines with very low HLA-A, HLA-B, and HLA-C expression, suggesting that HLA-E may indeed, in some cases, play a role by inhibiting NK lysis of cells that otherwise would be destroyed by NK cells. Finally, we provide evidence that the status of the immune system in the tumor-bearing animal is capable of defining the MHC profile of the tumor cells. In other words, MHC class I-negative metastatic colonies are produced in immunocompetent animals, and MHC class I-positive colonies in T-cell immunodeficient individuals.

PubMed Disclaimer

Figures

Fig. 1a

Fig. 1a

The primary tumor is composed originally of HLA-positive cells. During tumor development HLA-negative cells appear and are immunoselected by T-lymphocyte antitumor immune responses. b The metastatic nodes are composed of highly selected tumor clones with identical or sometimes different HLA class I deficiencies

Fig. 2

Fig. 2

The MHC class I phenotype of a metastatic tumor clone is dependent on the immune status of the host: metastatic nodes are MHC class I–negative in immunocompetent mice, and MHC class I–positive in T-cell–immunodeficient animals

Similar articles

Cited by

References

    1. Ahmed Am J Dermatopathol. 2002;24:330. doi: 10.1097/00000372-200208000-00009. - DOI - PubMed
    1. Algarra Int J Cancer. 1991;6:73.
    1. Bauer Science. 1999;285:727. doi: 10.1126/science.285.5428.727. - DOI - PubMed
    1. Boesen Clin Exp Immunol. 2000;121:1365. doi: 10.1046/j.1365-2249.2000.01292.x. - DOI - PMC - PubMed
    1. Boon Annu Rev Immunol. 1994;12:337. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources