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The tumor microenvironment disarms CD8 + T lymphocyte function via a miR-26a-EZH2 axis.

Authors :
Long H
Xiang T
Luo J
Li F
Lin R
Liu S
Jiang S
Hu C
Chen G
Wong E
Wan Y
Li QJ
Zhu B
Source :
Oncoimmunology [Oncoimmunology] 2016 Oct 18; Vol. 5 (12), pp. e1245267. Date of Electronic Publication: 2016 Oct 18 (Print Publication: 2016).
Publication Year :
2016

Abstract

One of the most important factors that limit the potency of CD8 <superscript>+</superscript> cytotoxic T lymphocyte (CTL) responses is the tumor microenvironment (TME). Here, we provide evidence that miR-26a is a negative regulator of CTL function in the TME. Specifically, we identified miR-26a as a crucial suppressor gene in CTLs from the TME, as we found that, miR-26a expression was elevated in CTLs to respond to TME secretome stimulation. CTLs from miR-26a-transgenic mice showed impaired IFNγ and granzyme B production in response to their cognate antigen. Conversely, we found that miR-26a inhibition in CTLs could effectively increase the cytotoxicity and suppress tumor growth. Mechanically, we identified EZH2 as a direct target of miR-26a. miR-26a and EZH2 expression were found to be inversely correlated in CTLs, and the inhibition of EZH2 in CTLs impairs CTL function. These functional correlations were validated in a cohort of non-small cell lung cancer patients, indicating that the miR-26a-EZH2 axis is clinically relevant. Our findings suggested that miR-26a silencing as a novel strategy to improve the efficacy of CTL-based cancer immunotherapy.

Details

Language :
English
ISSN :
2162-4011
Volume :
5
Issue :
12
Database :
MEDLINE
Journal :
Oncoimmunology
Publication Type :
Academic Journal
Accession number :
28123882
Full Text :
https://doi.org/10.1080/2162402X.2016.1245267