Journal: Blood Cancer Discovery
Article Title: Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells
doi: 10.1158/2643-3230.bcd-23-0020
Figure Lengend Snippet: Figure 2. Comparative immunopeptidome profiling identifies AML/LSC-associated HLA class I antigen targets. A, Saturation analysis of HLA class I-restricted peptide source proteins of the AML cohort. The mean number of unique source proteins (y-axis) for a given cohort size (number of samples, x-axis) has been calculated by 1,000 random samplings from the entirety of AML immunopeptidomes. The number of unique source protein identifica- tions (y-axis) is shown as a function of cumulative immunopeptidome analysis of AML samples (n = 47, x-axis). Exponential regression was used to extrapolate the maximum attainable coverage of different source proteins (dotted line, 11,193 proteins). The dashed line depicts the HLA-restricted peptide source proteome coverage achieved in the AML cohort (10,906 proteins). B, HLA class I allotype population coverage within the AML cohort com- pared with the world population (www.iedb.org). The frequencies of individuals within the world population carrying up to six HLA allotypes (x-axis) of the AML dataset are indicated as gray bars on the left y-axis. The cumulative percentage of population coverage is depicted as black dots on the right y-axis. C, Overlap analysis of HLA class I ligand identifications of primary AML samples (n = 47, curated immunopeptidome data) and benign samples (n = 332). D, Allotype-specific comparative immunopeptidome profiling based on the frequency of HLA-A*01–restricted peptide presentation in HLA-A*01–posi- tive AML (n = 14) and benign samples (n = 93). Frequencies of positive immunopeptidomes for the respective HLA ligand (x-axis) are indicated on the y-axis. HLA-A*01 ligands (n = 7,346) are depicted on the x-axis, sorted according to the frequency of AML and benign samples presenting the respective ligand. The box on the left highlights the subset of AML-associated antigens showing AML-exclusive, high frequent presentation. E, Overlap analysis of HLA class I ligand identifications of LSC samples (n = 10) with AML bulk (n = 47) and benign samples including CD34+-enriched HSPCs (n = 332). F, Pro- portion of all HLA class I and of HLA class I allotype-specific high frequent AML-associated peptides that are also presented on LSCs (AML/LSC shared antigens). N indicates the number of peptides. Abbreviations: ID, identification; IPep, immunopeptidome.
Article Snippet: MACS was performed with the human CD34 MultiSort (Miltenyi Biotec, catalog no. 130–056–701) and CD38 MicroBead Kits (Miltenyi Biotec, catalog no. 130–092–263).
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