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Defective HLA class I antigen processing machinery in cancer

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

Abstract

Malignant transformation of cells is frequently associated with defective HLA class I antigen processing machinery (APM) component expression. This abnormality may have functional relevance, since it may have a negative impact on tumor cell recognition by cognate T cells. Furthermore, HLA class I APM abnormalities appear to have clinical significance, since they are associated with poor prognosis in several malignant diseases and may play a role in the resistance to immune checkpoint inhibitor-based immunotherapy. In this paper, we have reviewed the literature describing abnormalities in HLA class I APM component expression in many types of cancer. These abnormalities have been reported in all types of cancer analyzed with a frequency ranging between a minimum of 35.8% in renal cancer and a maximum of 87.9% in thyroid cancer for HLA class I heavy chains. In addition, we have described the molecular mechanisms underlying defects in HLA class I APM component expression and function by malignant cells. Lastly, we have discussed the clinical significance of HLA class I APM component abnormalities in malignant tumors.

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Abbreviations

APM:

Antigen processing machinery

β2m:

β2-Microglobulin

EGFR:

Epidermal growth factor receptor

ERp57:

Endoplasmic reticulum protein 57

HDAC:

Histone deacetylase

HLA:

Human leukocyte antigen

LMP:

Low molecular weight polypeptide

mAb:

Monoclonal antibody

MAPK:

Mitogen-activated protein kinases

PD-1:

Programmed death 1 receptor

PD-L1:

Programmed death ligand 1

PDX:

Patient-derived xenograft

TAP:

Transporter associated with antigen processing

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Funding

This study was supported by National Cancer Institute (NCI) R21 (Grant no. CA164756), National Natural Science Foundation of China (Grant no. 81201948) and National Foundation of Chongqing (Grant No. cstc2012jjA10026).

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Authors and Affiliations

  1. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA

    Lei Cai, Theodoros Michelakos, Teppei Yamada, Song Fan, Xinhui Wang, Cristina R. Ferrone & Soldano Ferrone

  2. Department of Hepatobiliary, Southwest Hospital, Third Military Medical University, Chongqing, China

    Lei Cai

  3. Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Joseph H. Schwab

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  1. Lei Cai
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  2. Theodoros Michelakos
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All co-authors conceived, wrote and edited the manuscript.

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This paper is a Focussed Research Review based on a presentation given at the Fourteenth Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT) on Cancer Bio-Immunotherapy, held in Siena, Italy, 13th–15th October 2016. It is part of a series of Focussed Research Reviews and meeting report in Cancer Immunology, Immunotherapy.

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Cai, L., Michelakos, T., Yamada, T. et al. Defective HLA class I antigen processing machinery in cancer. Cancer Immunol Immunother 67, 999–1009 (2018). https://doi.org/10.1007/s00262-018-2131-2

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