“Hard” and “soft” lesions underlying the HLA class I alterations in cancer cells: Implications for immunotherapy

Authors

  • Federico Garrido,

    Corresponding author
    1. Departamento de Bioquímica, Biología Molecular 3 e Inmunología, Facultad de Medicina, Universidad de Granada, Granada, Spain
    2. Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Granada, Spain
    • Hospital Universitario Virgen de las Nieves, Servicio de Análisis Clínicos. Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain
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    • Fax: +34-958-020069

  • Teresa Cabrera,

    1. Departamento de Bioquímica, Biología Molecular 3 e Inmunología, Facultad de Medicina, Universidad de Granada, Granada, Spain
    2. Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Granada, Spain
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  • Natalia Aptsiauri

    1. Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Granada, Spain
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Abstract

The ability of cancer cells to escape from the natural or immunotherapy-induced antitumor immune response is often associated with alterations in the tumor cell surface expression of Major Histocompatibility Complex (MHC) Class I antigens. Considerable knowledge has been gained on the prevalence of various patterns of MHC Class I defects and the underlying molecular mechanisms in different types of cancer. In contrast, few data are available on the changes in MHC Class I expression happening during the course of cancer immunotherapy. We have recently proposed that the progression or regression of a tumor lesion in cancer patients undergoing immunotherapy could be predetermined by the molecular mechanism responsible for the MHC Class I alteration and not by the type of immunotherapy used, i.e., interleukin-2 (IL-2), Bacillus Calmette-Guèrin (BCG), interferon-alpha (IFN-α), peptides alone, dendritic cells loaded with peptides, protein-bound polysaccharide etc. If the molecular alteration responsible for the changes in MHC Class I expression is reversible by cytokines (“soft” lesion), the MHC Class I expression will be upregulated, the specific T cell–mediated response will increase and the lesion will regress. However, if the molecular defect is structural (“hard” lesion), the MHC Class I expression will remain low, the escape mechanism will prevail and the primary tumor or the metastatic lesion will progress. According to this idea, the nature of the preexisting MHC Class I lesion in the cancer cell has a crucial impact determining the final outcome of cancer immunotherapy. In this article, we discuss the importance of these two types of molecular mechanisms of MHC Class I–altered expression.

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