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

Lisa M Rimsza, Robin A. Roberts, Thomas P. Miller, Joseph M. Unger, Michael LeBlanc, Rita M. Braziel, Dennis D. Weisenberger, Wing C. Chan, H. Konrad Muller-Hermelink, Elaine S. Jaffe, Randy D. Gascoyne, Elias Campo, Deborah A. Fuchs, Catherine M. Spier, Richard I. Fisher, Jan Delabie, Andreas Rosenwald, Louis M. Staudt, Thomas M. Grogan

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)4251-4258
Number of pages8
JournalBlood
Volume103
Issue number11
DOIs
Publication statusPublished - Jun 1 2004

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ASJC Scopus subject areas

  • Hematology

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