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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

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Biomarkers for Immunotherapy of Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2055))

Abstract

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.

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Abbreviations

ACT:

Adoptive T cell therapy

APLNR:

Apelin receptor

APM:

Antigen processing machinery

BGN:

Biglycan

CNX:

Calnexin

CRC:

Colorectal cancer

CRT:

Calreticulin

CTL:

Cytotoxic T lymphocyte

ECM:

Extracellular matrix

EMT:

Epithelial–mesenchymal transition

ERAP:

ER-resident aminopeptidases

ER:

Endoplasmic reticulum

HC:

Heavy chain

HDAC:

Histone deacetylase

HDACi:

Histone deacetylase inhibitors

HLA:

Human leukocyte antigen

HNSCC:

Head and neck squamous cancer

iCP:

Immune checkpoint

iCPI:

Immune checkpoint inhibitor

IHC:

Immunohistochemistry

IFN:

Interferon

JAK:

Janus kinase

LOH:

Loss of heterozygosity

LMP:

Low molecular weight proteins

mAb:

Monoclonal antibody

miRNAs:

MicroRNAs

NLRC5:

NOD-like receptor caspase recruitment domain containing protein 5

NSCLC:

Non-small cell lung carcinoma

OS:

Overall survival

PLC:

Peptide loading complex

RBP:

RNA-binding proteins

RCC:

Renal cell carcinoma

SNP:

Single nucleotide polymorphisms

TA:

Tumor antigen

TAP:

Transporter associated with antigen processing

TIL:

Tumor-infiltrating lymphocyte

TNBC:

Triple negative breast cancer

tpn:

Tapasin

UCP2:

Uncoupling protein 2

β2-m:

β2-microglobulin

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Authors and Affiliations

  1. Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

    Barbara Seliger

  2. Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Soldano Ferrone

Authors
  1. Barbara Seliger
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  2. Soldano Ferrone
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Corresponding authors

Correspondence to Barbara Seliger or Soldano Ferrone .

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Editors and Affiliations

  1. NIH, National Cancer Institute, Bethesda, MD, USA

    Magdalena Thurin

  2. Nanostring Technologies, Seattle, WA, USA, ESSA Pharma, South San Francisco, CA, USA

    Alessandra Cesano

  3. Refuge Biotechnologies, Menlo Park, CA, USA

    Francesco M. Marincola

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Seliger, B., Ferrone, S. (2020). 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. In: Thurin, M., Cesano, A., Marincola, F. (eds) Biomarkers for Immunotherapy of Cancer. Methods in Molecular Biology, vol 2055. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9773-2_15

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  • DOI: https://doi.org/10.1007/978-1-4939-9773-2_15

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9772-5

  • Online ISBN: 978-1-4939-9773-2

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