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.