Expression levels of HLA-DR in acute myeloid leukemia: implications for antigenicity and clinical outcome
- 2 March 2021
- journal article
- research article
- Published by Informa UK Limited in Leukemia & Lymphoma
- Vol. 62 (8), 1907-1919
- https://doi.org/10.1080/10428194.2021.1885659
Abstract
Low human leukocyte antigen (HLA)-DR expression might compromise CD4+ T-cell-mediated anti-tumor immunity. Its immunological and clinical significance however remain undefined in non-promyelocytic acute myeloid leukemia (AML). Taking advantage of mass spectrometry-based immunopeptidome analysis of primary AML samples (n = 31), we studied the implications of low HLA-DR expression for antigen presentation and analyzed its association with disease characteristics and survival within a cohort of 399 AML patients. Remarkably, overall HLA-DR/DQ immunopeptidome diversity was preserved in AML with low HLA-DR expression (HLA-DRlow AML) and was associated with a shift in HLA-DR/DQ allotype abundances (HLA-DQ to HLA-DR/DQ ligand ratio 0.36 vs 0.19 in HLA-DRlow and HLA-DRhigh patients, respectively). Consistent with unimpaired antigenicity, survival was similar in HLA-DRlow and HLA-DRhigh patients. Demonstrating for the first time that overall HLA-DR/DQ antigen presentation is preserved in HLA-DRlow AML, our findings provide a rationale for the non-inferior outcome observed in HLA-DRlow AML patients.Keywords
This publication has 80 references indexed in Scilit:
- DNA methylation dysregulates and silences the HLA-DQ locus by altering chromatin architectureGenes & Immunity, 2011
- HLA-DP, HLA-DQ, and HLA-DR Have Different Requirements for Invariant Chain and HLA-DMJournal of Biological Chemistry, 2010
- CD4+ T-Cell Help in the Tumor Milieu Is Required for Recruitment and Cytolytic Function of CD8+ T LymphocytesCancer Research, 2010
- Regulation of major histocompatibility complex class II genesCurrent Opinion in Immunology, 2010
- Naive tumor-specific CD4+ T cells differentiated in vivo eradicate established melanomaThe Journal of Experimental Medicine, 2010
- Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hostsThe Journal of Experimental Medicine, 2010
- HLA‐DRneg patients without acute promyelocytic leukemia show distinct immunophenotypic, genetic, molecular, and cytomorphologic characteristics compared to acute promyelocytic leukemiaCytometry Part B: Clinical Cytometry, 2009
- Increased HLA-DMB Expression in the Tumor Epithelium Is Associated with Increased CTL Infiltration and Improved Prognosis in Advanced-Stage Serous Ovarian CancerClinical Cancer Research, 2008
- Multiple roles for CD4+ T cells in anti‐tumor immune responsesImmunological Reviews, 2008
- Regulation of MHC Class II Expression by Interferon-γ Mediated by the Transactivator Gene CIITAScience, 1994