The dual role of HLA-G in cancer.

Nathalie Rouas-Freiss,Edgardo D Carosella,Philippe Moreau,Joel Lemaoult

doi:10.1155/2014/359748

Abstract

We here review the current data on the role of HLA-G in cancer based on recent findings of an unexpected antitumor activity of HLA-G in hematological malignancies. For the past decade, HLA-G has been described as a tumor-escape mechanism favoring cancer progression, and blocking strategies have been proposed to counteract it. Aside from these numerous studies on solid tumors, recent data showed that HLA-G inhibits the proliferation of malignant B cells due to the interaction between HLA-G and its receptor ILT2, which mediates negative signaling on B cell proliferation. These results led to the conjecture that, according to the malignant cell type, HLA-G should be blocked or conversely induced to counteract tumor progression. In this context, we will here present (i) the dual role of HLA-G in solid and liquid tumors with special emphasis on (ii) the HLA-G active structures and their related ILT2 and ILT4 receptors and (iii) the current knowledge on regulatory mechanisms of HLA-G expression in tumors.

Highlights

Various immune effector cells are recruited to the tumor site, their antitumor functions are downregulated, largely in response to tumor-derived signals [1]
HLA-G is found to be expressed in solid tumors of high histological grades and advanced clinical stages [6, 7]; and (iii) the use of HLA-G as a prognostic marker has been proposed since HLA-G expression in biopsies and/or high levels of soluble HLA-G in plasma from patients have been significantly correlated with poor prognosis [6,7,8,9,10,11]
Based on the tolerogenic properties of HLA-G in the solid tumor context, blocking its expression and function may be considered as potential targets for antitumor therapy

Summary

Discrepancy in the Role of HLA-G in Solid and Liquid Tumors

Various immune effector cells are recruited to the tumor site, their antitumor functions are downregulated, largely in response to tumor-derived signals [1]. Analysis of crosstalk between tumor B cells, HLA-G+ mesenchymal stem cells, and osteoblasts in bone marrow may provide insights in understanding the mechanisms of tumor suppression in vivo in this biological compartment [40] These data indicate a innovative use of HLAG in cancer since we propose a radically opposite action of HLA-G if the tumor cell is an immune system cell, the function of which could be affected by HLA-G due to the presence of surface inhibitory receptors for HLA-G. We are describing the role of HLA-G on B-cell malignancies, we can expect a similar effect on malignant blood diseases involving T cells, NK cells, and monocytes since these fulfil the same criteria as B cells (i.e., cell-surface expression of HLA-G receptors with inhibitory functions) In agreement with this HLA-G antitumor activity in B cell malignancies, we previously showed that soluble HLAG inhibits the growth of erythropoietin (EPO)-independent colonies in patients suffering from polycythaemia vera [41, 42]. Current knowledge on the multiple HLA-G active structures and their potential use in therapy is described

The Multiple HLA-G Active Structures and Their Corresponding Receptors

The Control of HLA-G Expression

Findings

Concluding Remarks