Trogocytic intercellular membrane exchanges among hematological tumors.

Joel LeMaoult,Vera Rebmann,Magdalena Switala,Julien Caumartin,Marina Daouya,Bertrand Arnulf,Edgardo D Carosella

doi:10.1186/s13045-015-0114-8

Abstract

Trogocytosis is the transfer of plasma membrane fragments and the molecules they contain between one donor and one acceptor/acquirer cell. Through trogocytosis, acceptor cells temporarily display and use cell-surface molecules they do not express themselves, but borrow from other cells. Here, we investigated whether liquid tumors possessed a trogocytic capability, if immune escape molecules could be acquired by tumor cells, transferred between cells of the same tumor, and if this could benefit the tumor as a whole.For this, we investigated trogocytosis in hematological cell lines and freshly isolated hematological tumor cells. We demonstrate that hematological tumor lines possess a trogocytic capability that allows them to capture membranes that contain the immune-inhibitory molecule HLA-G from allogeneic as well as from autologous sources. We further show that freshly isolated hematological tumor cells also possess these capabilities. This work reports for the first time the trogocytic capabilities of liquid tumor cells and introduces the notion of immune escape strategy sharing among tumor cells through trogocytosis of membrane-bound immune-inhibitory molecules.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0114-8) contains supplementary material, which is available to authorized users.

Highlights

HLA-G is a tolerogenic molecule which expression was originally observed and characterized on throphoblasts
After autologous trogocytosis assay, 78.9% of the originally PKH67- and HLA-G1-negative acceptor U937 cells display PKH67-associated fluorescence, and 100% display HLA-G1-associated fluorescence. These results indicate that U937 acceptor cells have the capability to acquire membranes and membrane-bound HLA-G1 from allogeneic LCL-HLA-G1 cells and from autologous, HLA-G1-expressing U937 cells
Working with hematological cell lines and freshly isolated hematological tumors, we demonstrate here that trogocytic function was preserved in hematological tumors, that membrane exchanges happen in autologous situations, and are likely to occur in vivo

Summary

Introduction

HLA-G is a tolerogenic molecule which expression was originally observed and characterized on throphoblasts. HLA-G differs from classical MHC class I molecules by its genetic diversity, expression, structure, and functions. It is characterized by a relatively low allelic polymorphism and a highly restricted tissue distribution. HLA-G constitutive expression is mainly restricted to trophoblast cells [3], and to adult thymic medulla [5], pancreatic islets [6], and stem cells [7,8]. Recent studies have shown that HLA-G is capable of inducing the differentiation of regulatory T cells and antigen-presenting cells (APCs), which can inhibit immune responses themselves [20,23,25,26,27]

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Conclusion