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

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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.

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Acknowledgements

This work was supported in part by the Fondo de Investigaciones Sanitarias, Plan Nacional de Investigacion, through Project no. BSA 2001/3080, and by the Plan Andaluz de Investigacion. We thank K. Shashok for improving the English in the manuscript.

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Authors and Affiliations

  1. Departamento de Ciencias de La Salud, Universidad de Jaén, 23014, Jaén, Spain

    Ignacio Algarra

  2. Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Avda. de las Fuerzas Armadas 2, 18014, Granada, Spain

    Angel García-Lora, Teresa Cabrera, Francisco Ruiz-Cabello & Federico Garrido

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  1. Ignacio Algarra
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  2. Angel García-Lora
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  3. Teresa Cabrera
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  4. Francisco Ruiz-Cabello
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  5. Federico Garrido
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Correspondence to Federico Garrido.

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This article forms part of the Symposium in Writing “Tumor escape from the immune response,” published in Vol. 53.

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Algarra, I., García-Lora, A., Cabrera, T. et al. The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape. Cancer Immunol Immunother 53, 904–910 (2004). https://doi.org/10.1007/s00262-004-0517-9

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