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Antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B lymphocytes enhances the killing effect of cytotoxic T lymphocytes on tumor stem-like cells derived from cisplatin-resistant lung cancer cells.

ABSTRACT: The present study investigated whether antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B lymphocytes can enhance the killing effect of CD8+ cytotoxic T lymphocytes (CTLs) on lung stem-like cancer cells (SLCCs). The CTLs were generated using an accelerated co-cultured dendritic cells (DC) (acDC) assay by incubating human peripheral blood mononuclear cells (PBMCs) from non-small-cell lung cancer patients with antigen peptides of Oct4 and Sox2 in the presence of several DC-activating agents. CD154+ NIH3T3 cells prepared by CD154 lentiviral transfection were used as feeder layer to activate primary B cells (CD19+) obtained from PBMCs. Activated B cells were co-cultured with CTLs to present antigen peptides of Oct4 and Sox2. CTLs co-cultured with activated B cells were evaluated for the levels of secreted inflammatory cytokines using ELISA. In addition, the killing effect of the CTLs on SLCCs derived from cisplatin-resistant strain of human lung cancer cell line PC9 was evaluated by flow cytometry using CFSE labeling of the target cells. After the acDC assay, the PBMCs exhibited a significant (p<0.01) increase in the population of CD8+/CD3+ cells, indicating successful preparation of CTLs. The primary B cells cultured on the CD154+ NIH3T3 feeder layer resulted in significant (p<0.01) increase in the proportions of population expressing CD80, CD86, or HLA-A, indicating successful activation of the B cells. The co-culture of CTLs with CD154-activated B cells presenting the Oct4 and Sox2 peptides caused significant increase in the levels of secretory inflammatory cytokines and exhibited enhanced killing of the SLCCs derived from cisplatin-resistant PC9 cells. Antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B cells can enhance the killing effect of CTLs towards lung SLCCs.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5771344 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B lymphocytes enhances the killing effect of cytotoxic T lymphocytes on tumor stem-like cells derived from cisplatin-resistant lung cancer cells.

Zhang Xueyan X Zhang Yanwei Y Xu Jianlin J Wang Huimin H Zheng Xiaoxuan X Lou Yuqing Y Han Baohui B

Journal of Cancer 20180101 2

The present study investigated whether antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B lymphocytes can enhance the killing effect of CD8<sup>+</sup> cytotoxic T lymphocytes (CTLs) on lung stem-like cancer cells (SLCCs). The CTLs were generated using an accelerated co-cultured dendritic cells (DC) (acDC) assay by incubating human peripheral blood mononuclear cells (PBMCs) from non-small-cell lung cancer patients with antigen peptides of Oct4 and Sox2 in the presence of sev ...[more]

PMID: 29344283

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Project description:The identification of novel biomarkers and therapeutic targets in advanced cancer is critical for improving cancer diagnosis and therapeutics. Survivin (SV) is highly expressed predominantly in most cancer cells and tissues but is absent or undetectable in terminally differentiated normal adult tissues. Therefore, it functions as an almost universal tumor antigen. Peptides are short chains of amino acids linked by peptide bonds. To obtain novel SV decamers that are able to induce SV-specific cytotoxic T lymphocytes (CTLs) with a higher cytotoxic efficiency against cancer cells, major histocompatibility complex (MHC) peptide binding algorithms were conducted to predict nine modified SV95 decamers (from SV95-2 to SV95-10) based on the natural SV95-104 peptide sequence of ELTLGEFLKL (here defined as SV95-1). The fluorescent density of each SV95 peptide was determined by a MHC stability assay, followed by the generation of SV95-specific CTLs with each SV95 peptide (from SV95-1 to SV95-10) and human dendritic cells (DCs) loaded with Poly(lactic-co-glycolic) acid (PLGA) nanoparticles encapsulated with SV95 peptide. Finally, IFN-γ ELISpot and CytoTox 96® Non-Radioactive Cytotoxicity Assays were employed to verify their cytotoxic efficiency of the SV95-specific CTLs generated with the corresponding artificial antigen presenting cells (aAPCs) containing SV95 (SV95-1 to SV95-10) peptide. Furthermore, the cytotoxicity of the SV95 specific CTLs generated with nine mutated SV95 peptides was compared to the one generated with natural SV95-1 peptide and TIL2080 cells. The results indicated that the HLA-A2-restricted mutated SV95 epitope decamers (SV95-6 and SV95-7) showed significant higher binding ability compared to natural peptide SV95-1 in MHC stability assay. More importantly, SV95-specific CTLs with higher cytotoxicity were successfully induced with both SV95-6 and SV95-7 peptides, which significantly eliminated target cells (not only SV95-1 peptide pulsed T2 cells, but also both HLA-A2 and SV positive cancer cells) when compared to those generated with natural SV95-1 peptide and TIL2080 cells. These findings suggest that the SV95-6 and SV95-7 peptides are two novel HLA-A2-restricted CTL epitopes and may be useful for the immunotherapy for patients with survivin expressing cancer.

Dataset Information

Antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B lymphocytes enhances the killing effect of cytotoxic T lymphocytes on tumor stem-like cells derived from cisplatin-resistant lung cancer cells.

Publications

Antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B lymphocytes enhances the killing effect of cytotoxic T lymphocytes on tumor stem-like cells derived from cisplatin-resistant lung cancer cells.

Similar Datasets

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