Abstract
Partner of sld five 1 (PSF1) is an evolutionary conserved DNA replication factor involved in DNA replication in lower species, which is strongly expressed in normal stem cell populations and progenitor cell populations. Recently, we have investigated PSF1 functions in cancer cells and found that PSF1 plays a significant role in tumour growth. These findings provide initial evidence for the potential of PSF1 as a therapeutic target. Here, we reveal that PSF1 contains an immunogenic epitope suitable for an antitumour vaccine. We analysed PSF1 peptides eluted from affinity-purified human leukocyte antigen (HLA) by mass spectrometry and identified PSF179–87 peptide (YLYDRLLRI) that has the highest prediction score using an in silico algorithm. PSF179–87 peptide induced PSF1-specific cytotoxic T lymphocyte responses such as the production of interferon-γ and cytotoxicity. Because PSF1 is expressed in cancer cell populations and highly expressed in cancer stem cell populations, these data suggest that vaccination with PSF179–87 peptide may be a novel therapeutic strategy for cancer treatment.
Highlights
Cancer immunotherapy facilitates the inherent immune system by recognising molecular entities expressed on tumour cells, resulting in elimination of these cells
Partner of sld five 1 (PSF1) protein expression was observed in the original MDA-MB-231 cells; to identify PSF1-derived peptide captured on human leukocyte antigen (HLA) effectively, we overexpressed the PSF1 gene in MDA-MB-231-soluble HLA-A*02:01 (sHLA) cells by transient transfection using the MaxCyte electroporation transfection system
To identify human PSF1-specific epitopes that formed a complex with major histocompatibility complex (MHC) class I, transient expression of human PSF1 was induced in MDA-MB-231-sHLA cells
Summary
Cancer immunotherapy facilitates the inherent immune system by recognising molecular entities expressed on tumour cells, resulting in elimination of these cells. We have reported that high expression of PSF1 is associated with CSC properties[16], suggesting that PSF1 is a target molecule in CSCs and a candidate cancer-specific antigen. Significant technological improvements in genomics and proteomics along with supportive bioinformatics and in silico prediction tools have facilitated major breakthroughs in the delineation of the HLA peptidome that is the target of anti-cancer T cell responses[17]. Each having inherent advantages and disadvantages, both in silico-based prediction and direct MS-based approaches led to successful identification of the HLA peptidome for the development of cancer immunotherapy. The goal of the present study was to identify PSF1-derived peptides presented by HLA using two methodologies, in silico-based prediction and an MS-based approach. Our results suggest that PSF1 peptide generated in vitro shows the characteristics of an effective peptide vaccine against CSCs
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