Major histocompatibility complex abnormalities in non‐Hodgkin lymphomas

• Published in: British journal of haematology 2002-11, Vol.119 (2), p.417-424
• Main Authors: Drénou, Bernard, Le Friec, Gaelle, Bernard, Marc, Pangault, Céline, Grosset, Jean‐Marc, Lamy, Thierry, Fauchet, Renée, Amiot, Laurence
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Female; Flow Cytometry; Hematologic and hematopoietic diseases; Histocompatibility Antigens Class I - analysis; HLA Antigens - analysis; HLA class I; HLA-DR Antigens - analysis; HLA-G Antigens; HLA‐DR; HLA‐G; Humans; immune escape; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; lymphoma; Lymphoma, Non-Hodgkin - immunology; Male; Medical sciences; Middle Aged; Prospective Studies; Tumor Escape
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2002.03814.x

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.