HLA Class I Antigen Processing Machinery Defects in Cancer Cells—Frequency, Functional Significance, and Clinical Relevance with Special Emphasis on Their Role in T Cell-Based Immunotherapy of Malignant Disease

  • Barbara SeligerEmail author
  • Soldano FerroneEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 2055)


MHC class I antigen abnormalities have been shown to be one of the major immune escape mechanisms murine and human cancer cells utilize to avoid recognition and destruction by host immune system. This mechanism has clinical relevance, since it is associated with poor prognosis and/or reduced patients’ survival in many types of malignant diseases. The recent impressive clinical responses to T cell-based immunotherapies triggered by checkpoint inhibitors have rekindled tumor immunologists and clinical oncologists’ interest in the analysis of the human leukocyte antigen (HLA) class I antigen processing machinery (APM) expression and function in malignant cells. Abnormalities in the expression, regulation and/or function of components of this machinery have been associated with the development of resistances to T cell-based immunotherapies. In this review, following the description of the human leukocyte antigen (HLA) class I APM organization and function, the information related to the frequency of defects in HLA class I APM component expression in various types of cancer and the underlying molecular mechanisms is summarized. Then the impact of these defects on clinical response to T cell-based immunotherapies and strategies to revert this immune escape process are discussed.

Key words

Antigen processing machinery HLA class I Immune escape Immune response MHC Prognostic marker Tumor surveillance 



Adoptive T cell therapy


Apelin receptor


Antigen processing machinery






Colorectal cancer




Cytotoxic T lymphocyte


Extracellular matrix


Epithelial–mesenchymal transition


ER-resident aminopeptidases


Endoplasmic reticulum


Heavy chain


Histone deacetylase


Histone deacetylase inhibitors


Human leukocyte antigen


Head and neck squamous cancer


Immune checkpoint


Immune checkpoint inhibitor






Janus kinase


Loss of heterozygosity


Low molecular weight proteins


Monoclonal antibody




NOD-like receptor caspase recruitment domain containing protein 5


Non-small cell lung carcinoma


Overall survival


Peptide loading complex


RNA-binding proteins


Renal cell carcinoma


Single nucleotide polymorphisms


Tumor antigen


Transporter associated with antigen processing


Tumor-infiltrating lymphocyte


Triple negative breast cancer




Uncoupling protein 2




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© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Institute of Medical ImmunologyMartin Luther University Halle-WittenbergHalle (Saale)Germany
  2. 2.Division of Surgical Oncology, Department of Surgery, Massachusetts General HospitalHarvard Medical SchoolBostonUSA

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