Expression levels of HLA-DR in acute myeloid leukemia: implications for antigenicity and clinical outcome

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-DR^low 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-DR^low and HLA-DR^high patients, respectively). Consistent with unimpaired antigenicity, survival was similar in HLA-DR^low and HLA-DR^high patients. Demonstrating for the first time that overall HLA-DR/DQ antigen presentation is preserved in HLA-DR^low AML, our findings provide a rationale for the non-inferior outcome observed in HLA-DR^low AML patients.