Major histocompatibility complex abnormalities in non-Hodgkin lymphomas.
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.
Drénou
Bernard
B
Laboratoire Universitaire d'Hématologie et de la Biologie des Cellules Sanguines, UPRES EA 22.33, Rennes, France. bernard-drenou@univ-rennes1.fr
Le Friec
Gaelle
G
Bernard
Marc
M
Pangault
Céline
C
Grosset
Jean-Marc
JM
Lamy
Thierry
T
Fauchet
Renée
R
Amiot
Laurence
L
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
D006680:HLA Antigens; D006684:HLA-DR Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I