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Review
. 2021 Nov 11:12:791535.
doi: 10.3389/fimmu.2021.791535. eCollection 2021.

HLA-G/sHLA-G and HLA-G-Bearing Extracellular Vesicles in Cancers: Potential Role as Biomarkers

Peilong Li  1   2   3 , Nan Wang  4 , Yi Zhang  5 , Chuanxin Wang  1   2   3 , Lutao Du  1   2   3
Affiliations
Review

HLA-G/sHLA-G and HLA-G-Bearing Extracellular Vesicles in Cancers: Potential Role as Biomarkers

Peilong Li et al. Front Immunol. .

Abstract

As a non-classic major histocompatibility complex (MHC) class I molecule, human leukocyte antigen G (HLA-G) is expressed in fetal-maternal interface and immunoprivileged site only in healthy condition, and in pathological conditions such as cancer, it can be de novo expressed. It is now widely accepted that HLA-G is a key molecule in the process of immune escape of cancer cells, which is ubiquitously expressed in the tumor environment. This raises the possibility that it may play an adverse role in tumor immunity. The expression level of HLA-G has been demonstrated to be highly correlated with clinical parameters in many tumors, and its potential significance in the diagnosis and prognosis of cancer has been postulated. However, because HLA-G itself has up to seven different subtypes, and for some subtypes, detected antibodies are few or absent, it is hard to evaluate the actual expression of HLA-G in tumors. In the present work, we described (a) the structure and three main forms of HLA-G, (b) summarized the mechanism of HLA-G in the immune escape of tumor cells, (c) discussed the potential role of HLA-G as a tumor marker, and reviewed (d) the methods for detecting and quantifying HLA-G.

Keywords: HLA-G; biomarker; extracellular vesicles; immune escape; tumor.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
HLA-G protein isoforms and immune-inhibitory function.
Figure 2
Figure 2
HLA-G-bearing EVs with potential immunological and clinical relevance. NK cells and T cells acquire HLA-G from HLA-G+tumor cells or HLA-G+immune cells via the process of trogocytosis and/or EVs.
See this image and copyright information in PMC

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