Analysis of HLA class I alterations in tumors: choosing a strategy based on known patterns of underlying molecular mechanisms

Authors

  • T. Cabrera,

    1. Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Granada, Spain
    2. Departamento de Bioquimica, Biologia Molecular 3 e Inmunología, Facultad de Medicina, Universidad de Granada, Spain
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  • I. Maleno,

    1. Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Granada, Spain
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  • A. Collado,

    1. Unidad de Investigacion, Hospital Universitario Virgen de las Nieves, Granada, Spain
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  • M. A. Lopez Nevot,

    1. Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Granada, Spain
    2. Departamento de Bioquimica, Biologia Molecular 3 e Inmunología, Facultad de Medicina, Universidad de Granada, Spain
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  • B. D. Tait,

    1. Victorian Transplantation and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Australia
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  • F. Garrido

    Corresponding author
    1. Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Granada, Spain
    2. Departamento de Bioquimica, Biologia Molecular 3 e Inmunología, Facultad de Medicina, Universidad de Granada, Spain
      Federico Garrido
      Hospital Universitario Virgen de las Nieves
      Dept. de Análisis Clínicos
      Avd. Fuerzas Armadas 2
      18014 Granada
      Spain
      Tel: 34 958 020319
      Fax: 34 958 283147
      e-mail: federico.garrido.sspa@juntadeandalucia.es
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Federico Garrido
Hospital Universitario Virgen de las Nieves
Dept. de Análisis Clínicos
Avd. Fuerzas Armadas 2
18014 Granada
Spain
Tel: 34 958 020319
Fax: 34 958 283147
e-mail: federico.garrido.sspa@juntadeandalucia.es

Abstract

The application of peptide-based immunotherapy in the treatment of cancer has known limitations in patients with loss or downregulation of human leukocyte antigen (HLA) class I expression on tumor cells. These alterations diminish the ability of cancer cells to present tumor peptides to T cells and therefore lead to failure of peptide-based cancer vaccination. Abnormal expression of HLA class I molecules in malignant cells is a frequent event that ranges from total loss of class I molecules to partial loss of HLA-specific haplotypes or alleles. Different mechanisms underlie these alterations and might require different therapeutic approaches. A complete characterization of molecular defects may suggest strategies for the selection and follow-up of patients undergoing T-cell based immunotherapy. Moreover, a precise identification of the mechanism leading to HLA class I defects in patients with cancer will help develop new, personalized patient-tailored treatment protocols. Here, we describe several examples showing the necessity and feasibility of making detailed individual analysis of HLA alteration mechanisms based on previously described molecular patterns in different types of malignancy. We recommend using this approach, at least in some patients, to enhance the therapeutic benefit of cancer immunotherapy.

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