Upstream open reading frames regulate proto-oncogene translation and encode HLA-presented immunogenic tumor antigens

ABSTRACT: Upstream open reading frames (uORFs) represent translational control elements within eukaryotic transcript leader sequences. Recent data showed that uORFs can encode for biologically active proteins and human leucocyte antigen (HLA)-presented peptides and suggest their potential role in cancer cell development and survival. However, it is so far unclear if uORF-encoded peptides could serve as tumor-associated antigen targets and thus also play a role in cancer immune surveillance. Combining mass spectrometry-based immunopeptidome analysis in primary tumor and healthy tissues and evaluation of proto-oncogene-associated uORF-mediated translational control we here identified a panel of HLA-presented tumor-associated uORF-derived antigens. These uORF-derived tumor antigens were further shown to induce multifunctional antigen-specific T cells, validating their suitability as antigen targets for T cell-based cancer immunotherapy. Our data further unravel the role of uORF-encoded peptides in malignant disease, suggesting uORF-derived tumor-associated antigens as targets for anti-cancer immune surveillance and immunotherapy development.

INSTRUMENT(S): LTQ Orbitrap, Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Peripheral Blood Mononuclear Cell, Blood

DISEASE(S): Chronic Lymphocytic Leukemia,Acute Myeloid Leukemia

SUBMITTER: Annika Nelde  

LAB HEAD: Juliane S. Walz

PROVIDER: PXD025716 | Pride | 2022-04-04

REPOSITORIES: Pride