Low GILT expression is associated with poor patient survival in diffuse large B-cell lymphoma

Hannah Phipps-Yonas, Haiyan Cui, Noemi Sebastiao, Patrick S. Brunhoeber, Ellen Haddock, Martin J. Deymier, Wolfram Klapper, Lonnie Lybarger, Denise Roe, Karen Taraszka Hastings

Research output: Contribution to journalArticle

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Abstract

The major histocompatibility complex (MHC) class II-restricted antigen processing pathway presents antigenic peptides acquired in the endocytic route for the activation of CD4+ T cells. Multiple cancers express MHC class II, which may influence the anti-tumor immune response and patient outcome. Low MHC class II expression is associated with poor survival in diffuse large B-cell lymphoma (DLBCL), the most common form of aggressive non-Hodgkin lymphoma. Therefore, we investigated whether gamma-interferon-inducible lysosomal thiol reductase (GILT), an upstream component of the MHC class II-restricted antigen processing pathway that is not regulated by the transcription factor class II transactivator, may be important in DLBCL biology. GILT reduces protein disulfide bonds in the endocytic compartment, exposing additional epitopes for binding to MHC class II and facilitating antigen presentation. In each of four independent gene expression profiling cohorts with a total of 585 DLBCL patients, low GILT expression was significantly associated with poor overall survival. In contrast, low expression of a classical MHC class II gene, HLA-DRA, was associated with poor survival in one of four cohorts. The association of low GILT expression with poor survival was independent of established clinical and molecular prognostic factors, the International Prognostic Index and the cell of origin classification, respectively. Immunohistochemical analysis of GILT expression in 96 DLBCL cases demonstrated variation in GILT protein expression within tumor cells which correlated strongly with GILT mRNA expression. These studies identify a novel association between GILT expression and clinical outcome in lymphoma. Our findings underscore the role of antigen processing in DLBCL and suggest that molecules targeting this pathway warrant investigation as potential therapeutics.

Original languageEnglish (US)
Article numberArticle 425
JournalFrontiers in Immunology
Volume4
Issue numberDEC
DOIs
StatePublished - 2013

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Sulfhydryl Compounds
Interferon-gamma
Oxidoreductases
Major Histocompatibility Complex
Survival
Antigen Presentation
Histocompatibility Antigens Class II
HLA-DR alpha-Chains
Neoplasms
MHC Class II Genes
Gene Expression Profiling
Disulfides
Non-Hodgkin's Lymphoma
Cell Biology
Epitopes
Lymphoma
Proteins
B-Lymphocytes
Transcription Factors

Keywords

  • Antigen processing and presentation
  • Diffuse large B cell lymphoma
  • GILT
  • MHC class II
  • Tumor immunology

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Phipps-Yonas, H., Cui, H., Sebastiao, N., Brunhoeber, P. S., Haddock, E., Deymier, M. J., ... Hastings, K. T. (2013). Low GILT expression is associated with poor patient survival in diffuse large B-cell lymphoma. Frontiers in Immunology, 4(DEC), [Article 425]. https://doi.org/10.3389/fimmu.2013.00425

Low GILT expression is associated with poor patient survival in diffuse large B-cell lymphoma. / Phipps-Yonas, Hannah; Cui, Haiyan; Sebastiao, Noemi; Brunhoeber, Patrick S.; Haddock, Ellen; Deymier, Martin J.; Klapper, Wolfram; Lybarger, Lonnie; Roe, Denise; Hastings, Karen Taraszka.

In: Frontiers in Immunology, Vol. 4, No. DEC, Article 425, 2013.

Research output: Contribution to journalArticle

Phipps-Yonas, H, Cui, H, Sebastiao, N, Brunhoeber, PS, Haddock, E, Deymier, MJ, Klapper, W, Lybarger, L, Roe, D & Hastings, KT 2013, 'Low GILT expression is associated with poor patient survival in diffuse large B-cell lymphoma', Frontiers in Immunology, vol. 4, no. DEC, Article 425. https://doi.org/10.3389/fimmu.2013.00425
Phipps-Yonas H, Cui H, Sebastiao N, Brunhoeber PS, Haddock E, Deymier MJ et al. Low GILT expression is associated with poor patient survival in diffuse large B-cell lymphoma. Frontiers in Immunology. 2013;4(DEC). Article 425. https://doi.org/10.3389/fimmu.2013.00425
Phipps-Yonas, Hannah ; Cui, Haiyan ; Sebastiao, Noemi ; Brunhoeber, Patrick S. ; Haddock, Ellen ; Deymier, Martin J. ; Klapper, Wolfram ; Lybarger, Lonnie ; Roe, Denise ; Hastings, Karen Taraszka. / Low GILT expression is associated with poor patient survival in diffuse large B-cell lymphoma. In: Frontiers in Immunology. 2013 ; Vol. 4, No. DEC.
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AU - Haddock, Ellen

AU - Deymier, Martin J.

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AU - Hastings, Karen Taraszka

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