Soluble HLA-G molecules are increased in lymphoproliferative disorders

The immunomodulatory properties of soluble human leukocyte antigen G (sHLA-G) explain its potential interest in malignancies. HLA-G frequently transcribed in lymphoproliferative disorders is rarely expressed at cell surface. In this article, we will demonstrate that the plasmatic level of soluble HLA-G was significantly increased in 70% of B chronic lymphocytic leukemia, 53% of non-Hodgkin B lymphoma (B-NHL), and 45% of T-NHL. To explain this variable secretion, the HLA-G secreting cell was searched and was identified as tumoral T4 lymphocytes only in one patient with Sezary syndrome. To approach the mechanisms involved in sHLA-G secretion, the potential role of cytokines has been studied in vitro on T lymphomas. A significant increase of sHLA-G level is observed after activation by cytokines associated with a small increase in the quantity of transcripts using real-time polymerase chain reaction, suggesting an involvement of both transcriptional and post-transcriptional mechanisms. Western Blot analysis reveals no evident variation of the protein expression whatever the conditions, suggesting a continuous secretion and a low intracellular storage. The frequency of the sHLA-G secretion associated to its inhibiting role on T cells and natural killer cells during tumoral lymphoid malignancies suggests a potential role of these molecules as escape mechanism from antitumoral response.