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

Peilong Li,Yi Zhang,Nan Wang,Chuanxin Wang,Lutao Du

doi:10.3389/fimmu.2021.791535

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.

Highlights

As early as 1983, human leukocyte antigen G (HLA-G) is first observed on the cytotrophoblast at the fetal-maternal interface [1]
For ascites caused by gynecological tumors and gastrointestinal tumors, the levels of related tumor markers CEA and CA199 are elevated in malignant ascites, while its specificity and sensitivity are significantly lower compared with soluble HLA-G (sHLA-G) [139]
In ovarian cancer (OC), sHLA-G1/G5 is negatively correlated with CD3-/CD56+ subgroups and CD4+ CD45RO+ memory cells, suggesting that sHLA-G plays a role in the tumor microenvironment by upregulating T-reg cells and down-regulating natural killer (NK) cells [39]

Summary

Introduction

As early as 1983, human leukocyte antigen G (HLA-G) is first observed on the cytotrophoblast at the fetal-maternal interface [1]. The plasma levels (median[range]) of sHLA-G were significantly increased compared with healthy controls (34 ng/mL [3.6–160] vs 14 ng/mL [0–98]). ELISA shows that the plasma levels of sHLA-G in patients with liver cancer are higher compared with the control group [134].

Results

Conclusion