HLA-G can be transfered via trogocytosis from leukemic cells to T cells in chronic lymphocytic leukemia

In chronic lymphocytic leukemia (CLL) immune escape mechanism allows leukemia cells to proliferate and expand and it might also be responsible for disease progression. Some molecules involved in the regulation of an immune system might represent prognostic value for CLL patients. Among numerous immune escape mechanisms it was shown that the expression of human leukocyte antigen G (HLA-G) might represent one of the agents damaging cellular immune response. In the present study, the expression of the HLA-G molecule and ILT-2 receptor on the surface of leukemic cells, as well as a plasma concentration of soluble HLA-G (sHLA-G) was evaluated. Also, we investigated whether HLA-G could be transferred from leukemic cells to T cells by the mechanism of trogocytosis. We showed higher proportion of leukemic cells expressing HLA-G and increased levels of sHLA-G in CLL patients compared to that of B-cells in healthy volunteers (HVs). Results of our work showed a time-dependent increase in HLA-G expression on CD4+ T cells co-incubated with HLA-G-positive CD19+ cells. Longer coincubation times did significantly increase these proportions (p < 0.001). We have shown that a higher proportion of HLA-G-expressing CD4+ T cells correlated with the clinical stage of the disease according to the Rai classification. Interestingly, we found a higher CD4+HLA-G+ percentage in the group with unmutated immunoglobulin heavy chain variable region (IGHV) genes compared to the group with mutated IGHV gene after 48 h co-culture. In summary, increasing evidence has revealed that, in addition to HLA-G expressed on tumor cells, intercellular transfer of HLA-G among cancer cells and immune cells through trogocytosis plays important roles in mechanism of immune escape, disease progression and poor clinical outcome.