Τίτλος:
ERAP2 Inhibition Induces Cell‐Surface Presentation by MOLT‐4 Leukemia Cancer Cells of Many Novel and Potentially Antigenic Peptides
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Recent studies have linked the activity of ER aminopeptidase 2 (ERAP2) to increased efficacy of immune‐checkpoint inhibitor cancer immunotherapy, suggesting that pharmacological inhibition of ERAP2 could have important therapeutic implications. To explore the effects of ERAP2 inhibition on the immunopeptidome of cancer cells, we treated MOLT‐4 T lymphoblast leukemia cells with a recently developed selective ERAP2 inhibitor, isolated Major Histocompatibility class I molecules (MHCI), and sequenced bound peptides by liquid chromatography tandem mass spectrometry. Inhibitor treatment induced significant shifts on the immunopeptidome so that more than 20% of detected peptides were either novel or significantly upregulated. Most of the inhibitor‐induced peptides were 9mers and had sequence motifs and predicted affinity consistent with being optimal ligands for at least one of the MHCI alleles carried by MOLT‐4 cells. Such inhibitor‐induced peptides could serve as triggers for novel cytotoxic responses against cancer cells and synergize with the therapeutic effect of immune‐checkpoint inhibitors. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Temponeras, I.
Stamatakis, G.
Samiotaki, M.
Georgiadis, D.
Pratsinis, H.
Panayotou, G.
Stratikos, E.
Περιοδικό:
International Journal of Molecular Sciences
Λέξεις-κλειδιά:
aminopeptidase; ERAP2 protein, human; HLA antigen class 1; peptide; phosphinic acid derivative, acute lymphoblastic leukemia; antigen presentation; cell proliferation; cell survival; chemistry; drug effect; high performance liquid chromatography; human; immunology; tandem mass spectrometry; tumor cell line, Aminopeptidases; Antigen Presentation; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chromatography, High Pressure Liquid; Histocompatibility Antigens Class I; Humans; Peptides; Phosphinic Acids; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tandem Mass Spectrometry
DOI:
10.3390/ijms23031913
