Literature DB >> 27381730

Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin.

Jiong-Huang Chen1, Jian-Yang Xiang1, Guo-Ping Ding1, Li-Ping Cao1.   

Abstract

OBJECTIVE: The aim of our study is to observe the impact of cholangiocarcinoma-derived exosomes on the antitumor activities of cytokine-induced killer (CIK) cells and then demonstrate the appropriate mechanism.
METHODS: Tumor-derived exosomes (TEXs), which are derived from RBE cells (human cholangiocarcinoma line), were collected by ultracentrifugation. CIK cells induced from peripheral blood were stimulated by TEXs. Fluorescence-activated cell sorting (FACS) was performed to determine the phenotypes of TEX-CIK and N-CIK (normal CIK) cells. The concentrations of tumor necrosis factor-α (TNF-α) and perforin in the culture medium supernatant were examined by using an enzyme-linked immunosorbent assay (ELISA) kit. A CCK-8 kit was used to evaluate the cytotoxic activity of the CIK cells to the RBE cell line.
RESULTS: The concentrations of TNF-α and perforin of the group TEX-CIK were 138.61 pg/ml and 2.41 ng/ml, respectively, lower than those of the group N-CIK 194.08 pg/ml (P<0.01) and 3.39 ng/ml (P<0.05). The killing rate of the group TEX-CIK was 33.35%, lower than that of the group N-CIK (47.35% (P<0.01)). The population of CD3(+), CD8(+), NK (CD56(+)), and CD3(+)CD56(+) cells decreased in the TEX-CIK group ((63.2±6.8)%, (2.5±1.0)%, (0.53±0.49)%, (0.45±0.42)%) compared with the N-CIK group ((90.3±7.3)%, (65.7±3.3)%, (4.2±1.2)%, (15.2±2.7)%), P<0.01.
CONCLUSIONS: Our results suggest that RBE cells-derived exosomes inhibit the antitumor activity of CIK cells by down-regulating the population of CD3(+), CD8(+), NK (CD56(+)), and CD3(+)CD56(+) cells and the secretion of TNF-α and perforin. TEX may play an important role in cholangiocarcinoma immune escape.

Entities:  

Keywords:  Cholangiocarcinoma; Cytokine-induced killer cells; Immune escape; Tumor-derived exosomes

Mesh:

Substances:

Year:  2016        PMID: 27381730      PMCID: PMC4940629          DOI: 10.1631/jzus.B1500266

Source DB:  PubMed          Journal:  J Zhejiang Univ Sci B        ISSN: 1673-1581            Impact factor:   3.066


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