HLA-G Antigen Expression Is Associated with a More Aggressive, Unfavorable Outcome and Immunosuppression in Chronic Lymphocytic Leukemia.

Background: The human leukocyte antigen (HLA)-G molecule exhibits limited tissue distribution and exerts multiple immunoregulatory functions. Recent studies indicate an ectopic up-regulation in tumor cells which may favor their escape from antitumor immune responses. The role of HLA-G in B cell chronic lymphocytic leukemia (B-CLL) has not been defined.

Experimental design: HLA-G expression was studied retrospectively in circulating B-CLL cells from 47 patients by flow cytometry using the MEM/G9 monoclonal antibody.

Results: The proportion of leukemic cells expressing HLA-G varied from 1% to 54%. Patients with < 23% HLA-G positive cells (according to ROC analysis; designated as the HLA-G negative group) had a significantly longer progression-free survival (PFS) time than patients with > 23% of positive cells (median PFS 120 versus 23 months, p=0.0001). Multivariate analysis revealed that HLA-G expression (hazard ratio 4.81; p=0.002) was next to the initial staging according to Binet (hazard ratio 8.6; p=0.0001) the best independent prognostic factor compared to other known prognostic factors like ZAP-70 status (hazard ratio 3.6; p=0.029) or CD38 status (hazard ratio 1.83; p=0.37). Humoral and cellular immunosuppression was significantly more prominent in HLA-G positive as compared to HLA-G negative patients group (median immunglobuline G (g/l) 4.3 versus 7.3; median total T-cells (per μl) 824 versus 2540).

Conclusions: In B-CLL the level of HLA-G expression is correlated with the degree of immunosuppression and prognosis. To our knowledge this is the first report that describes an association of HLA-G antigen expression and the course of the disease in B-CLL patients. Thus, HLA-G may contribute to the impairment of immune responses against tumor cells and infections. These findings need to be confirmed in a prospective study.