HLA-G expression is associated with an unfavorable outcome and immunodeficiency in chronic lymphocytic leukemia.
The human leukocyte antigen G (HLA-G) molecule exhibits limited tissue distribution and exerts multiple immunoregulatory functions. Recent studies indicate an ectopic up-regulation in tumor cells that 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. HLA-G expression was studied retrospectively in circulating B-CLL cells from 47 patients by flow cytometry using the anti-HLA-E specific monoclonal antibody MEM/G9. The proportion of leukemic cells expressing HLA-G varied from 1% to 54%. Patients with 23% or fewer HLA-G-positive cells (according to receiver operating characteristics [ROC] analysis; designated as HLA-G-negative group) had a significantly longer progression-free survival (PFS) time than patients with more than 23% positive cells (median PFS: 120 versus 23 months; P = .0001). In multivariate analysis, HLA-G expression (hazard ratio: 4.8; P = .002) was an even better independent prognostic factor than the zeta-associated protein 70 (ZAP-70) or CD38 status. Humoral and cellular immunosuppression were significantly more prominent in the HLA-G-positive compared with the HLA-G-negative patient group. In B-CLL, the level of HLA-G expression is correlated with the degree of immunosuppression and prognosis. HLA-G may contribute to the impairment of immune responses against tumor cells and infections. Thus, these findings need to be confirmed in a prospective study.
Nückel
Holger
H
Department of Hematology, University of Duisburg-Essen, Germany. holger.nueckel@uniessen.de
Rebmann
Vera
V
Dürig
Jan
J
Dührsen
Ulrich
U
Grosse-Wilde
Hans
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D006680:HLA Antigens / Q000096:biosynthesis* / Q000097:blood; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000473:pathology; D007165:Immunosuppression Therapy / Q000706:statistics & numerical data; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000473:pathology
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G