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

  • Focussed Research Review
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

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.

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Acknowledgments

The authors would like to thank Dr. Natalia Aptsiauri for helpful discussion. A. García-Lora was supported by Fundación Progreso y Salud and FIS-Research Contract CP03/0111. This study was partially supported by Grants from the Fondo de Investigaciones Sanitarias (FIS, CP03/0111; PI 08/1265), Red Genómica del Cancer RTICCC (RETIC RD 06/020), Consejeria de Salud and Plan Andaluz de Investigación (PAI, Group CTS-143 and projects CTS-695, CTS-3952, CVI-4740) from the Junta de Andalucia, in Spain; by the ENACT project (LSHC-CT-2004-503306) and the Cancer Immunotherapy project (OJ 2004/c158, 18234) from the European Community, and by Kureha Chemical Industry, Tokyo, Japan.

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Authors and Affiliations

  1. Servicio de Análisis Clínicos and Inmunología, Hospital Universitario Virgen de las Nieves, Av. de las Fuerzas Armadas 2, 18014, Granada, Spain

    Federico Garrido & Angel M. García-Lora

  2. Departamento de Bioquímica y Biología Molecular III e Inmunología, Universidad de Granada, Granada, Spain

    Federico Garrido

  3. Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén, Spain

    Ignacio Algarra

Authors
  1. Federico Garrido
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  2. Ignacio Algarra
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  3. Angel M. García-Lora
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Corresponding author

Correspondence to Angel M. García-Lora.

Additional information

This paper is a Focussed Research Review based on a presentation given at the Ninth International Conference on Progress in Vaccination against Cancer (PIVAC 9), held in Sofia, Bulgaria, 8–10 October 2009.

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Garrido, F., Algarra, I. & García-Lora, A.M. The escape of cancer from T lymphocytes: immunoselection of MHC class I loss variants harboring structural-irreversible “hard” lesions. Cancer Immunol Immunother 59, 1601–1606 (2010). https://doi.org/10.1007/s00262-010-0893-2

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