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

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-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.

Keywords:

• Acute myeloid leukemia
• AML
• HLA-DR
• mass spectrometry
• immunopeptidome
• HLA class II

Acknowledgments

The authors thank Ulrike Schmidt and Claudia Falkenburger for excellent technical support.

Disclosure statement

H.-G.R. is shareholder of Immatics Biotechnologies GmbH and Curevac AG. The other authors declare no conflict of interest.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Additional information

Funding

This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Grant WA 4608/1-2; the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy under Grant EXC2180-390900677; the Wilhelm Sander Stiftung under Grant 2016.177.2; the José Carreras Leukämie-Stiftung under Grant DJCLS 05 R/2017 and the Fortüne Program of the University of Tübingen under Grant 2451-0-0 and 2581-0-0.