Proteomics

Dataset Information

0

AML HLA Ligandome reveals mutated NPM1 as a recurrent neoantigen


ABSTRACT: Somatic mutations in cancer are a potential source of cancer specific neoantigens. Acute myeloid leukemia (AML) has common recurrent mutations shared between patients in addition to private mutations specific to individuals. We hypothesized that neoantigens derived from recurrent shared mutations would be attractive targets for future immunotherapy and sought to study the Class I and II HLA ligandomes of thirteen primary AML tumor samples and two AML cell lines (OCI-AML3 and MV4-11) using mass spectrometry. We identified two endogenous, mutation-bearing HLA Class I ligands from NPM1, which are predicted to bind the common HLA haplotypes, HLA-A*03:01 and HLA-A*02:01 respectively. We further derived CD8+ T cells from healthy donor peripheral blood samples which bound mutant-peptide loaded A*03:01 and A*02:01 tetramers, suggesting a new source of NPM1 mutation-specific T cell receptors (TCRs) for future evaluation. Since NPM1 is mutated in approximately one-third of patients with AML, the finding of endogenous NPM1 neoantigens supports future studies evaluating immunotherapeutic approaches against this target, for this subset of patients with AML.

INSTRUMENT(S): Orbitrap Fusion Lumos, LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Peripheral Blood, Myeloid Cell

DISEASE(S): Acute Myeloid Leukemia

SUBMITTER: Niclas Olsson  

LAB HEAD: Joshua E Elias

PROVIDER: PXD012083 | Pride | 2019-07-17

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
FL0012549.raw Raw
FL0012553.raw Raw
FL0012563.raw Raw
FL0012567.raw Raw
FL0012581.raw Raw
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Somatic mutations in cancer are a potential source of cancer specific neoantigens. Acute myeloid leukemia (AML) has common recurrent mutations shared between patients in addition to private mutations specific to individuals. We hypothesized that neoantigens derived from recurrent shared mutations would be attractive targets for future immunotherapeutic approaches. Here we sought to study the HLA Class I and II immunopeptidome of thirteen primary AML tumor samples and two AML cell lines (OCI-AML3  ...[more]

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