title: Major histocompatibility complex abnormalities in non-Hodgkin lymphomas.
abstract: An optimal antitumoral immune response requires the participation of both CD8 and CD4 T lymphocytes, which are activated by peptide antigen presentation via human leucocyte antigen (HLA) class I and class II molecules respectively. Loss of HLA molecules has been observed in different malignancies, and provides a mechanism for escape from immune surveillance. Furthermore, HLA-G, a class Ib molecule, is considered to be an immune tolerance-inducing molecule. HLA-G expression on tumour cells could provide a further mechanism for immune escape. To determine the frequency and the pattern of HLA defects in non-Hodgkin lymphomas (NHL), HLA expression was prospectively studied in 614 NHL cases, using flow cytometry. Furthermore, HLA-G expression was tested in 50 cases, including 20 cases selected on the basis of their defective HLA class I expression. In 64 cases (10.4%), lymphomatous cells exhibited lower HLA class I mean fluorescence intensity compared with reactive cells. Their characteristics were (1) the diversity of histological entities; (2) the significant frequency of relapse or transformation; (3) the increased incidence of high-grade NHL compared with low-grade; and (4) the severity of the class I defect in 50% of the cases, mainly in high-grade NHL. A defect in HLA-DR expression was always associated with a severe class I defect (12 cases; 2%). The HLA-G protein was detected in three class I defective cases. These HLA alterations frequently appeared as a secondary event at relapse or at transformation, suggesting a direct role in lymphomagenesis.
authors.affiliation: Laboratoire Universitaire d'Hématologie et de la Biologie des Cellules Sanguines, UPRES EA 22.33, Rennes, France. bernard-drenou@univ-rennes1.fr
authors.forename: Bernard
authors.initials: B
authors.lastname: Drénou
authors.forename: Gaelle
authors.initials: G
authors.lastname: Le Friec
authors.forename: Marc
authors.initials: M
authors.lastname: Bernard
authors.forename: Céline
authors.initials: C
authors.lastname: Pangault
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Grosset
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamy
authors.forename: Renée
authors.initials: R
authors.lastname: Fauchet
authors.forename: Laurence
authors.initials: L
authors.lastname: Amiot
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019139:Tumor Escape
chemical_list: D006680:HLA Antigens; D006684:HLA-DR Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I