EpCAM peptide-primed dendritic cell vaccination confers significant anti-tumor immunity in hepatocellular carcinoma cells.

Yoo Jin Choi,Seong-Joon Park,Hee Sung Park,Kwang Mo Yang,You-Soo Park,Kyu Heo,Daotai Nie

doi:10.1371/journal.pone.0190638

Yoo Jin Choi, Seong-Joon Park + Show 5 more

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https://doi.org/10.1371/journal.pone.0190638

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Journal: PloS one	Publication Date: Jan 3, 2018
Citations: 33	License type: CC BY 4.0

Affiliation: Dongnam Institute of Radiological & Medical Sciences

Abstract

Cancer stem-like cells (CSCs) may play a key role in tumor initiation, self-renewal, differentiation, and resistance to current treatments. Dendritic cells (DCs) play a vital role in host immune reactions as well as antigen presentation. In this study, we explored the suitability of using CSC peptides as antigen sources for DC vaccination against human breast cancer and hepatocellular carcinoma (HCC) with the aim of achieving CSC targeting and enhancing anti-tumor immunity. CD44 is used as a CSC marker for breast cancer and EpCAM is used as a CSC marker for HCC. We selected CD44 and EpCAM peptides that bind to HLA-A2 molecules on the basis of their binding affinity, as determined by a peptide-T2 binding assay. Our data showed that CSCs express high levels of tumor-associated antigens (TAAs) as well as major histocompatibility complex (MHC) molecules. Pulsing DCs with CD44 and EpCAM peptides resulted in the efficient generation of mature DCs (mDCs), thus enhancing T cell stimulation and generating potent cytotoxic T lymphocytes (CTLs). The activation of CSC peptide-specific immune responses by the DC vaccine in combination with standard chemotherapy may provide better clinical outcomes in advanced carcinomas.

Highlights

Tumor cells express antigens that can be recognized by the immune system of their host
Cancer stem-like cells (CSCs) are a subset of cancer cells bearing stem cell features such as self-renewal and the ability to differentiate into progeny cells, and play a pivotal role in cancer initiation, progression and recurrence [17]
Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that are present in small numbers in all body tissues [25], and they are responsible for capturing and presenting antigens for the initiation of T cell immune responses

Summary

Introduction

Tumor cells express antigens that can be recognized by the immune system of their host. Cancer patients can be inoculated by these tumor-associated antigens (TAAs) to induce systemic immune responses that may result in the destruction of various cancers. This procedure is defined as active immunotherapy, or vaccination [1]. Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) that exist in the immune system [2, 3]. DC vaccines aim to stimulate cancer-specific effector T cells to eradicate tumor cells and to stimulate immunological memory to control cancer recurrence.

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