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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

  • Barbara SeligerEmail author
  • Soldano FerroneEmail author
Protocol
Part of the Methods in Molecular Biology book series (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.

Key words

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

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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Copyright information

© 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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