Histone deacetylase inhibition up-regulates MHC class I to facilitate cytotoxic T lymphocyte-mediated tumor cell killing in glioma cells.

Abstract:

:Background: Immune cells recognize tumor antigens presented on major histocompatibility complex class I (MHC-I) molecule. Increase of MHC-I molecular expression makes tumor cells more susceptible to lysis by immune cells. Methods: Tumor lysate vaccine was prepared to damage glioma cells including cell lines and primary cultured cells from surgical samples. The enhanced effect of histone deacetylase inhibitors (HDACi) to tumor lysate vaccine was observed. The expressions of MHC-I pathway molecules were detected by flow cytometry and western blot after HDACi treatment. Cell apoptosis and cell lysis were measured following blocking cytotoxic T lymphocyte (CTL) pathway. Tumor size and mice survival were analyzed in combinative treatment with HDACi and tumor lysate. Results: HDACi up-regulated the expressions of MHC-I pathway molecules, and enhanced the recognition and killing of immune cells, which was activated by tumor lysate. Activated antigen specific immune responses regulated CTL activity, and HDACi promoted immune response through cytotoxic effect of CTL. Anti-tumor effect of tumor lysate pulse immunogenicity in vivo was elevated by HDACi due to up-regulation of antigen presentation. Conclusions: Our study showed that HDACi enhanced recognition of glioma cell by immune cells and sensitivity of tumor immunotherapy, and improved the anti-tumor effect of tumor lysate vaccine through activating CTL immune response. These pharmacological molecular mechanisms of increasing immune recognition suggest that epigenetic modulation is a promising strategy for sensitizing immunotherapy for glioma treatment.

journal_name

J Cancer

journal_title

Journal of Cancer

authors

Sun T,Li Y,Yang W,Wu H,Li X,Huang Y,Zhou Y,Du Z

doi

10.7150/jca.34471

subject

Has Abstract

pub_date

2019-09-07 00:00:00

pages

5638-5645

issue

23

issn

1837-9664

pii

jcav10p5638

journal_volume

10

pub_type

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