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

Research output: Contribution to journalArticle

220 Scopus citations

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
StatePublished - Jun 1 2004

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Rimsza, L. M., Roberts, R. A., Miller, T. P., Unger, J. M., LeBlanc, M., Braziel, R. M., Weisenberger, D. D., Chan, W. C., Muller-Hermelink, H. K., Jaffe, E. S., Gascoyne, R. D., Campo, E., Fuchs, D. A., Spier, C. M., Fisher, R. I., Delabie, J., Rosenwald, A., Staudt, L. M., & Grogan, T. M. (2004). 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. Blood, 103(11), 4251-4258. https://doi.org/10.1182/blood-2003-07-2365