Focussed Research Review

Cancer Immunology, Immunotherapy

, Volume 59, Issue 10, pp 1601-1606

First online:

The escape of cancer from T lymphocytes: immunoselection of MHC class I loss variants harboring structural-irreversible “hard” lesions

  • Federico GarridoAffiliated withServicio de Análisis Clínicos and Inmunología, Hospital Universitario Virgen de las NievesDepartamento de Bioquímica y Biología Molecular III e Inmunología, Universidad de Granada
  • , Ignacio AlgarraAffiliated withDepartamento de Ciencias de la Salud, Universidad de Jaén
  • , Angel M. García-LoraAffiliated withServicio de Análisis Clínicos and Inmunología, Hospital Universitario Virgen de las Nieves Email author 

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The discovery of tumor antigens recognized by T lymphocytes has stimulated the development of a variety of cancer treatment protocols aimed at enhancing antitumor-specific T cell responses and tumor rejection. However, immunotherapy-mediated regression of established tumors and clearly positive clinical response to such treatment has not been achieved yet despite the induction of T cells directed against tumor antigens. The failure of the modern immunotherapy protocols can be explained by different tumor escape mechanisms that have been defined in various types of malignancy. The loss or downregulation of MHC class I antigens in tumor cells is one of the best analyzed mechanisms. In this review, we show experimental evidence obtained in our laboratory on human tumors and in a mouse cancer model suggesting that the molecular mechanism responsible for the MHC class I alteration in tumor cells might have a crucial impact on tumor recovery of normal H-2/HLA expression during the natural history of tumor development or after immunotherapy. When the preexisting molecular lesion underlying tumor MHC class I alteration is reversible (regulatory or soft), class I expression can be recovered leading to regression of tumor lesion. In contrast, if the HLA class I alteration is irreversible in nature (structural or hard), the lesion will progress killing the host. This is a new vision of the role of MHC class I alteration in tumors that can explain the failure of immunotherapy in a variety of different clinical protocols.


MHC Cancer Immunoselection Hard lesions Soft lesions Immunotherapy