Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2017; 23(24): 4390-4398
Published online Jun 28, 2017. doi: 10.3748/wjg.v23.i24.4390
Gastric cancer-derived heat shock protein-gp96 peptide complex enhances dendritic cell activation
Wen-Wen Lu, Hong Zhang, You-Ming Li, Feng Ji
Wen-Wen Lu, Department of Geriatrics, the First Affiliated Hospital of Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Hong Zhang, You-Ming Li, Feng Ji, Department of Gastroenterology, the First Affiliated Hospital of Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Author contributions: Lu WW and Zhang H designed the research; Lu WW and Li YM performed the research; Zhang H contributed analytical tools; Ji F analyzed the data; Lu WW and Zhang H wrote the paper; Li YM and Ji F revised the manuscript.
Supported by Science and Technology Department of Zhejiang Province, No. 2008C33064.
Institutional review board statement: This study was reviewed and approved by the Institutional Ethnics Committee of the First Affiliated Hospital of Zhejiang University, Hangzhou, China.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the First Affiliated Hospital of Zhejiang University, Hangzhou, China.
Conflict-of-interest statement: The authors declare that no conflict of interest exists in this study.
Data sharing statement: The anonymized dataset is available from the corresponding author (hongzhang1013@163.com) and will be provided on request after obtaining all authors’ agreement.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hong Zhang, Professor, Department of Gastroenterology, the First Affiliated Hospital of Zhejiang University, No. 79, Qingchun Road, Hangzhou 310003, Zhejiang Province, China. hongzhang1013@163.com
Telephone: +86-571-87236532 Fax: +86-571-87236611
Received: November 13, 2016
Peer-review started: November 15, 2016
First decision: January 10, 2017
Revised: February 9, 2017
Accepted: April 12, 2017
Article in press: April 12, 2017
Published online: June 28, 2017
Abstract
AIM

To investigate the role of heat shock protein (HSP)-glycoprotein (gp)96 in dendritic cells (DCs) and lymphocytes induction in gastric cancer (GC).

METHODS

Human GC cell lines KATOIII, MKN-28 and SGC-7901 were infected with adenovirus gp96 at a multiplicity of infection of 100. gp96-GC antigen peptide complexes were purified. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, lactate dehydrogenase (LDH) release assay and enzyme-linked immunosorbent assay were used to determine allo-reactive T cell stimulation, natural killer (NK) cell activity and expression of cytokines (such as interleukin (IL)-10, IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α), respectively. Effect of cytotoxic T lymphocyte (CTL) on DCs incubated with HSP-gp96 was also evaluated by LDH release. All assays were performed in triplicate and the average values were reported. Comparison between groups was conducted using Student’s t test.

RESULTS

T cells incubated with HSP-gp96 exhibited a marked increase in proliferation in a dose-dependent manner (P < 0.05). NK cell activity after gp96-GC peptide complex treatment was significantly higher than that after antigen peptide treatment (P < 0.05). The activity of CTLs incubated with DCs from three GC cells lines was obviously higher than that stimulated by GC antigen at ratios of 50: 1, 25: 1, 10: 1, and 5: 1 (P < 0.05). Furthermore, the secretion of TNF-α, IL-10, IL-12 (P70) and IFN-γ markedly increased after incubation with HSP-gp96 (P < 0.05).

CONCLUSION

HSP-gp96 promotes T cell response, enhances DC antigen presentation and induces cytokine secretion, as well. HSP-gp96 has potential as immunotherapy for elimination of residual GC cells.

Keywords: Gastric cancer, Heat shock protein gp96, T lymphocytes, Dendritic cells, Natural killer cells, Cytotoxic T lymphocytes, Immunization therapy

Core tip: Heat shock protein (HSP)- glycoprotein (gp)96 was studied to evaluate its capacity to stimulate immune cells. Compared with gastric cancer (GC)-derived peptide, purified gp96-GC peptide complex markedly increased proliferation of allogeneic normal T lymphocytes, and activity of natural killer cells and cytotoxic T lymphocytes. Therefore, HSP-gp96 derived from GC cells has immunotherapeutic potential for elimination of residual GC cells.