Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project

• Published in: Blood 2004-06, Vol.103 (11), p.4251-4258
• Main Authors: Rimsza, Lisa M., Roberts, Robin A., Miller, Thomas P., Unger, Joseph M., LeBlanc, Michael, Braziel, Rita M., Weisenberger, Dennis D., Chan, Wing C., Muller-Hermelink, H. Konrad, Jaffe, Elaine S., Gascoyne, Randy D., Campo, Elias, Fuchs, Deborah A., Spier, Catherine M., Fisher, Richard I., Delabie, Jan, Rosenwald, Andreas, Staudt, Louis M., Grogan, Thomas M.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Follow-Up Studies; Hematologic and hematopoietic diseases; Histocompatibility Antigens Class II - genetics; HLA-DR Antigens - genetics; Humans; Immunologic Surveillance; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - mortality; Medical sciences; Oligonucleotide Array Sequence Analysis; Prognosis; Survival Analysis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-07-2365

The Leukemia and Lymphoma Molecular Profiling Project recently published results from DNA microarray analyses of 240 diffuse large B-cell lymphomas (DLBCLs). Four gene expression “signatures” were identified as correlated with patient outcome, including the major histocompatibility complex (MHC) class II genes (eg, HLA-DRA) which correlated with better survival. We further analyzed the effects of HLA-DRA on survival and correlated gene expression with protein status and tumor-infiltrating lymphocytes. The 5-year overall survival was 24% in the lowest 10% of HLA-DRA expression, 37% in the 10% to 25% group, 50% in the 25% to 50% group, and 55% for patients in the highest 50%. Further analysis demonstrated that the hazard ratio of death was a nonlinear function of HLA-DRA expression. Adjustment for the International Prognostic Index did not alter the impact of HLA-DRA on survival. Other MHC class II genes were found to predict survival similarly. Microarray HLA-DRA expression correlated with the presence or absence of human leukocyte antigen-DR (HLA-DR) protein in 20 of 22 cases assessed. Fewer tumor-infiltrating CD8+ T cells were detected in MHC class II-negative cases compared with positive cases (2.8% versus 11.0%; P = .001), supporting the hypothesis that loss of tumor immunosurveillance has a devastating effect on patient outcome in DLBCL. (Blood. 2004; 103:4251-4258)